Biol. Chem.
2017; 398(10): 1095–1108
Review
Christophe Glorieuxa and Pedro Buc Calderon*
Catalase, a remarkable enzyme: targeting
the oldest antioxidant enzyme to find a new
cancer treatment approach
DOI 10.1515/hsz-2017-0131
Received March 13, 2017; accepted April 4, 2017; previously published
online April 6, 2017
Abstract: This review is centered on the antioxidant enzyme
catalase and will present different aspects of this particu-
lar protein. Among them: historical discovery, biological
functions, types of catalases and recent data with regard
to molecular mechanisms regulating its expression. The
main goal is to understand the biological consequences of
chronic exposure of cells to hydrogen peroxide leading to
cellular adaptation. Such issues are of the utmost impor-
tance with potential therapeutic extrapolation for various
pathologies. Catalase is a key enzyme in the metabolism of
H2O2 and reactive nitrogen species, and its expression and
localization is markedly altered in tumors. The molecular
mechanisms regulating the expression of catalase, the old-
est known and first discovered antioxidant enzyme, are
not completely elucidated. As cancer cells are character-
ized by an increased production of reactive oxygen spe-
cies (ROS) and a rather altered expression of antioxidant
enzymes, these characteristics represent an advantage in
terms of cell proliferation. Meanwhile, they render cancer
cells particularly sensitive to an oxidant insult. In this con-
text, targeting the redox status of cancer cells by modulat-
ing catalase expression is emerging as a novel approach to
potentiate chemotherapy.
Keywords: antioxidant enzyme; cancer; catalase; catalase
regulation; hydrogen peroxide; pro-oxidant therapy.
a
Present address: Sun Yat-Sen University Cancer Center, State Key
Laboratory of Oncology in South China, Collaborative Innovation
Center of Cancer Medicine, 510275 Guangzhou, China.
*Corresponding author: Pedro Buc Calderon, Metabolism and
Nutrition Research Group, Louvain Drug Research Institute,
Université Catholique de Louvain, Avenue E. Mounier 73, 1200
Brussels, Belgium; and Facultad de Ciencias de la Salud,
Universidad Arturo Prat, 1100000 Iquique, Chile, e-mail: pedro.
buccalderon@uclouvain.be
Christophe Glorieux: Metabolism and Nutrition Research Group,
Louvain Drug Research Institute, Université Catholique de Louvain,
Avenue E. Mounier 73, 1200 Brussels, Belgium
Historical view
The origin of catalase (EC 1.11.1.6), the enzyme that metab-
olizes H2O2 but also reacts with a multitude of other sub-
strates, can be traced back to the 19th century (Figure 1)
when Thénard discovered H2O2 and suspected that its tissue
degradation in living organisms was the result of a ‘special’
substance activity (Thénard, 1811). Schönbein showed that
a ‘ferment’ can detoxify H2O2 (Schönbein, 1863) and later
on Loew gave the name ‘catalase’ to the enzyme converting
H2O2 into water and oxygen (Loew, 1900). Loew found the
presence of this enzyme in many organisms ranging from
plants to mammals. In the 1920s, Warburg and c­ oworkers
demonstrated, by using cyanide as enzyme inhibitor, that
the active site of catalase contains an iron atom (Warburg,
1923). Furthermore, Stern showed that the hemin group of
the enzyme can react with compounds such as cyanides,
sulfides, fluorides and he also showed that the enzyme
active group had a ferric complex identical to the protopor-
phyrin found in the hemoglobin of red blood cells (Stern,
1937). Thereafter, Sumner and Dounce (1937) purified and
crystallized bovine catalase.
The advances in biochemistry facilitated further elu-
cidation about the mechanisms of the ‘catalase’ enzy-
matic reaction. Thus, the work carried out by Chance’s
lab led to the discovery of the formation of the ‘Com-
pound I’ that occurred during the reaction between cata-
lase and the first molecule of H2O2. A few years later, he
also discovered the ‘compounds II and III’ (Chance, 1948,
1949; Chance et al., 1952). In the 1960s, it was elucidated
the role of key residues in the active site of the enzyme,
such as the distal histidine, and their importance for the
stabilization of the tertiary structure was discussed by
Nakatani (1961). In 1970, catalase Compound I was iden-
tified in intact eukaryotic cells, proving the existence of
H2O2 in normal aerobic metabolism (Sies and Chance,
1970). Kirkman and Gaetani reported that NADPH was
the enzyme cofactor bound to catalase (1984), which
was further confirmed following X-ray analysis of cata-
lase structures (Fita and Rossmann, 1985a). Finally,
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM
1096      C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach
Figure 1: Time line of catalase main discoveries and findings.
Modified from Sies (2017).
recombinant phage clones containing the human cata-
lase gene were isolated and characterized (Quan et  al.,
1986) and the use of molecular biology techniques have
led to major advances in the understanding of catalase
regulation mechanisms and the role that this enzyme
could play in numerous biological processes.
In this context, Nenoi et al. (2001) reported that in the
upstream catalase promoter, there is a region containing
CCAAT and GGGCGG boxes where transcription factors
like Nuclear factor Y (NF-Y) and Specificity protein 1 (Sp1)
can bind to the catalase promoter regulating the transcrip-
tional activation of the human catalase gene. Recently,
Glorieux et al. (2016a) identified a new regulatory region
in the human catalase promoter, in which chromatin
remodeling is required to regulate catalase expression by
retinoic acid receptor alpha (RARα) and JunB transcrip-
tion factors. This novel regulatory mechanism is involved
during cancer cells adaptation to chronic exposure to H2O2
and may have therapeutic consequences for various dis-
eases and metabolic disorders.
Types of catalases
With the increasing number of complete sequences availa-
ble, distinct homologies were detected and catalases came
to be classified in three groups based on their structure and
function. The first and the second group contain heme-
containing enzymes, namely typical or true catalases and
catalase-peroxidases, whereas the third group contains
(non-heme) manganese catalases (Zamocky and Koller,
1999; Zamocky et al., 2008, 2010).
Typical catalases
The members of this largest group are found in aerobically
respiring organisms. In contrast, in anaerobic ­bacteria,
catalases proteins are generally not expressed. Most of
these catalases are homotetramers, between 200 and
340 kDa in size and contain four prosthetic groups. In the
majority of true catalases, a ferric protoporphyrin IX was
found in the active center (namely heme b, similar to the
prosthetic group of human hemoglobin). Some variants
do exist such as ‘heme d’ groups which can reside in some
typical catalases.
Following phylogenetic analyses the typical cata-
lases can also be divided into three main clades. Clade 1
contains bacterial, algal and plant catalases with small-
sub­unit size (55–69 kDa) using heme b as the prosthetic
group. Clade 2 regroups bacterial and fungal catalases
and has a large subunit size (75–84  kDa), with heme d
as the prosthetic group and an additional ‘flavodoxin-
like’ domain. Clade 3 is the most abundant subfamily;
catalases from this subgroup are found in archaebacte-
rial, fungi, protists, plants and animals. The human cata-
lase belongs to this clade and is characterized by a small
subunit (62 kDa), with heme b as its prosthetic group and
NADPH as cofactor.
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM
 C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach      1097
Catalase-peroxidases
These proteins have been found in fungi, archeobacteria
and bacteria. Their molecular weight varies between 120
and 340 kDa and they are generally homodimers. The cat-
alase activity (degrading hydrogen peroxide) is less effi-
cient than in typical catalases but catalase-peroxidases
have a better affinity for their substrate H2O2. Catalase-per-
oxidases are also significantly more sensitive than typical
catalases to inactivation by pH and temperature. The
well-known horseradish peroxidase, currently employed
in immunoblotting experiments, is one example of
catalase-peroxidase.
Manganese catalases
These enzymes have been found exclusively in bacteria.
Manganese catalases utilize two manganese ions in the
active site, they can form oligomeric structures measuring
between 170 and 210 kDa and have no significant homol-
ogy with either typical catalases or catalase-peroxidases.
The catalytic reaction is completely different to other
types of catalases. The dimanganese core is equally stable
Mn2+–Mn2+ or Mn3+–Mn3+. Like typical catalases, the cata-
lase reaction occurs in two-step.
1st step: H2O2 + Mn −Mn (2H ) → Mn −Mn + 2 H2O
2+ 2+ + 3+ 3+
2nd step: H2O2 + Mn −Mn → Mn −Mn (2H ) + O2
3+ 3+ 2+ 2+ +
Sum of reactions: H2 O2 + H2 O2 → 2 H2O + O2
Structure of human catalase
Human catalase contains four identical subunits of
62 kDa, each subunit containing four distinct domains and
one prosthetic heme group (Nagem et al., 1999; Zamocky
and Koller, 1999; Putnam et al., 2000). The four domains
include: (1) a N-terminal arm which contains a distal histi-
dine, an essential amino acid for the catalase reaction; (2)
a β-barrel domain that contains eight β-barrels arranged
in an antiparallel fashion with six α-helical insertions,
conferring the hydrophobic core of the protein neces-
sary for the tri-dimensional structure of the enzyme; (3)
a connection domain which contains the tyrosine residue
that binds the heme group; and finally (4) an α-helical
domains, which is important for NADPH binding.
Although amino acid sequences do not have high
identities between all typical catalases, the tridimensional
structure is highly conserved. The tertiary structure of the
β-barrel domain, the connection domain and the zone
neighboring the distal histidine are highly conserved.
The α-helical domain is moderately conserved between
species and some typical catalases do not bind the cofac-
tor NADPH.
The investigation of inhibitory mechanisms by
which cyanide and 3-amino-1,2,4-triazole (ATA) inhibit
human catalase allowed to understand the enzyme activ-
ity (Putnam et  al., 2000). Cyanide nitrogen blocks heme
access to other potential ligands. It interacts with the
distal histidine and an asparagine residue suggesting that
it competes with hydrogen peroxide for heme binding.
Meanwhile, ATA interacts with the distal histidine leading
to an adduct formation and thereby blocks the catalase
reaction.
Mechanism of ‘catalase’ reaction
During the enzymatic reaction leading to H2O2 destruction,
catalase is first oxidized to a hypervalent iron intermedi-
ate, known as compound I (Cpd I), which is then reduced
back to the resting state by a second H2O2 molecule.
1st reaction: Enz (Porf-FeIII ) + H2 O2 →
Cpd I (Porf •+ -FeIV =O) + H2O
2nd reaction: Cpd I (Porf •+ -FeIV =O) + H2O2 →
Enz (Porf-FeIII ) + H2 O + O2
Sum of reactions: H2 O2 + H2O2 → 2 H2O + O2
The first reaction is characterized by the oxidation of the
heme protein by a single H2O2 molecule leading to the
formation of Cpd I, an oxoferryl porphyrin cation radical
(Jones and Dunford, 2005). Once Cpd I is formed, it reacts
rapidly with a second molecule of H2O2 to generate H2O
and O2 in a two-electron redox process. This second reac-
tion is particularly efficient in some catalases compared
to other heme proteins such as myoglobin (Matsui et al.,
1999). Labeling studies have shown that both H2O and
O2 molecules are formed from the same molecule of H2O2
(Vlasits et al., 2007). Fita and Rossmann (1985b) proposed
that two molecules of H2O2 were sequentially transferred
to the oxoferryl group of Cpd I, where the distal histidine
residue plays a role of acid-base catalyst. Although muta-
tion of distal histidine suppresses the ability to form Cpd I
(Nakatani, 1961), some authors claimed that reaction
occurs as a direct mechanism and histidine does not play
a crucial role in catalysis (Kato et al., 2004).
In the presence of one-electron donors (such as
phenols, ferrocyanide, salicylic acid, NO, superoxide
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM
1098      C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach
anions) and low H2O2 concentrations, Cpd I may undergo
a one-electron reduction towards the inactive compound
II (Cpd II) intermediate, which transforms back to the
resting state through another one-electron reduction step
(reviewed in Bauer, 2015). Both Cpd I and Cpd II are gen-
erally described as an oxoferryl-heme species (Rovira,
2005). In the case of Cpd I, the porphyrin bears a cation
radical (O=FeIV-heme˙+), while Cpd II lacks the porphy-
rin cation radical (O=FeIV-heme). Thus, Cpd II is best
described as a hydroxoferryl bond (HO-FeIV-heme) instead
of the traditional oxoferryl species, consistent with the
fact that a proton is released upon conversion of Cpd I to
Cpd II:
Cpd I + AH (one-electron donor) →
Cpd II(Por-FeIV = O and Por-FeIV -OH)
At higher H2O2 concentrations, NADPH prevents the gen-
eration of Cpd II by participating in a two-electron reduc-
tion process (Kirkman et  al., 1999). In the presence of
another one-electron donor, Cpd II will return to a resting
state. But in presence of a H2O2 molecule, Cpd II will be
transformed back to compound III (Cpd III), an inactive
intermediate (Gabdoulline et  al., 2003). In this interme-
diate state, iron is at an oxyferrous state (O2-FeII-heme).
Then, Cpd III goes back to a resting state or leads to the
inactivation of the catalase.
Cpd II + AH → Enz (Por-FeIII ) resting state
Cpd II + H2O2 → Cpd III (Por-FeII -O2 )
Cpd III → Enz (Por-FeIII ) or inactivation
Cellular and tissue catalase
distribution
Regarding catalase localization within the cell, it should
be noted that catalase is mainly located in peroxisomes
because it contains a sequence signal recognized by some
peroxisome receptors. Contrary to mitochondria, proteins
located within peroxisomes are all of nuclear origin and
should be imported. Indeed, it is generally accepted that
catalase monomers are imported into peroxisomes where
tetramerization and heme addition occurs (Lazarow and
De Duve, 1973). The apoprotein (monomer) enters into the
peroxisome by a peroxisome-targeting signal sequence
(PTS) present on the carboxy-terminal tail of catalase. The
most common targeting signal is the SKL (serine-lysine-
leucine) but catalase is characterized by a different signal,
namely the KANL (lysine-alanine-asparagine-leucine)
signal (Purdue and Lazarow, 1996). Proteins bearing these
signals are recognized by the PTS1 receptor, called PEX5p
for humans. Some diseases related to defects in peroxi-
some biogenesis, such as Zellweger syndrome, are char-
acterized by mutations in the PEX5p receptor and cellular
H2O2 overproduction due to a catalase default import in
peroxisomes (Wanders et al., 1984). This syndrome is most
commonly called ‘the syndrome of empty peroxisome’. It
has been shown that overexpressing receptor mutants in
PEX5-deficient CHO cells, drastically reduce the import of
proteins such as catalase (Shimozawa et al., 1999). Some
authors have observed that catalase with the SKL signal
and not KANL had a better import capacity and could be
transported into the peroxisome even in the case of muta-
tions in the PTS1 receptor (Koepke et al., 2007). It has been
shown that PEX5p recognizes catalase which is already
folded and interacts with other receptors such as PEX13p
for proper import into the peroxisome (Otera and Fujiki,
2012). Studies are underway to validate, through clinical
trials, whether catalase SKL has a therapeutic potential for
diseases with peroxisome biogenesis disorders. Recently,
it has been reported that PEX19p, an essential protein for
peroxisome biogenesis, interacts with Valosin-contain-
ing protein (VCP) and regulates the catalase cytoplasmic
localization, a potential feedback mechanism modulating
H2O2 levels (Murakami et al., 2013).
Interestingly, the existence of a cytosolic catalase,
in its active tetrameric conformation, has been reported
(­Middelkoop et al., 1993) with varied percentage from one
cell type to another, and different function to peroxisome
catalase. Indeed, catalase may bind cytosolic proteins such
as Grb2 and SHP2, to protect them from potential oxidative
damage (Yano et al., 2004a,b). These proteins are linked to
the membrane by a pleckstrin homology (PH) domain, so
it is common to find catalase in fractions including mem-
brane proteins and membrane-associated proteins. In this
context, it has been shown that catalase can be localized
at the cytoplasmic membrane, specifically at the surface
of cancer cells (Bauer, 2012). This locally high expression
of catalase on the membrane of tumor cells is in line with
the findings by Deichman’s group that showed that tumor
progression in vivo is dependent on increased resistance
towards exogenous H2O2 (Deichman, 2000, 2002). Further-
more, localized expression of catalase on the membrane
of tumor cells is not in disagreement with the finding of
lower total catalase concentration in malignant cells, as
the membrane comprises a minority of the total cellular
material.
These observations open the way for new anti-can-
cer therapies targeting catalase with specific antibodies
(Bauer, 2012; Bauer and Motz, 2016) or exogenous singlet
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM
 C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach      1099
oxygen (Riethmüller et al., 2015; Bauer and Graves, 2016)
to induce apoptosis by reactivation of intercellular HOCl
and/or NO/peroxynitrite signaling after catalase inhibi-
tion or inactivation. Furthermore, the modulation of the
intracellular NO concentration has been shown to lead to
the generation of cell-derived singlet oxygen that inacti-
vates tumor cell protective catalase and reactivates inter-
cellular ROS/RNS-mediated apoptosis-inducing signaling
(Bauer, 2015; Scheit and Bauer, 2015).
In addition to classical intracellular catalase and
membrane-associated catalase of tumor cells (Heinzel-
mann and Bauer, 2010; Böhm et al., 2015), the release of
soluble catalase from tumor cells has also been reported
(Sandstrom and Buttke, 1993; Moran et  al., 2002; Böhm
et al., 2015). This soluble extracellular catalase was pro-
tective for the tumor cells.
Finally, catalase has been also localized in the mito-
chondria of rat cardiomyocytes (Radi et al., 1991).
The human catalase is expressed in every organ and
the highest levels of activity are measured in the liver,
kidney and red blood cells (Winternitz and Meloy, 1908).
In erythrocytes, a high production of H2O2 is generated
due to oxygen transport and catalase is responsible for
more than 50% of the H2O2 turnover (Mueller et al., 1997).
Biological functions of catalase
and related diseases
The first function assigned to catalase is the dismutation
of H2O2 into oxygen and water without consummation of
endogenous reducing equivalents, an important role in
cell defense against oxidative damage by H2O2. To note
that H2O2 is not only toxic by its ability to form other ROS,
like hydroxyl radical through the Fenton reaction (Fenton,
1894) but as was nicely recently reviewed by Sies, H2O2
acting as a second messenger is involved in many biologi-
cal processes including changes of morphology, prolifera-
tion, signaling (i.e. NF-κB), apoptosis, etc (Sies, 2017). In
addition to its dominant ‘catalatic’ activity (decomposi-
tion of H2O2), catalase can also act in its peroxidatic mode,
i.e. decomposition of small substrates such as methanol,
formate, azide, hydroperoxides (Sies, 1974; Chance et al.,
1979; Johansson and Borg, 1988), and in case of ethanol,
it is also capable of oxidize it to acetaldehyde contributing
to its liver metabolism (Keilin and Hartree, 1945; Thurman
et al., 1972; Oshino et al., 1973). It has also been reported
that catalase may decompose peroxynitrite (Gebicka and
Didik, 2009; Heinzelmann and Bauer, 2010), oxidize
nitric oxide to nitrite (Wink and Mitchell, 1998; Brunelli
et al., 2001). A discrete balance between oxidation of NO
by compound I of catalase and inhibition of catalase by
NO through formation of a CAT-FeIIINO complex has been
reported (Brown, 1995). Catalase also exhibits low oxidase
activity (O2-dependent oxidation of organic substrates)
(Vetrano et al., 2005). Thus, catalase may also have addi-
tional roles such as the detoxification or activation of toxic
and anti-tumor compounds. For instance, catalase has
been detected in mouse oocytes most likely to protect the
genome from oxidative damage during meiotic matura-
tion (Park et al., 2016).
Within this framework, several studies have shown
a change in catalase expression in cancer cells became
resistant to chemotherapies (Akman et  al., 1990; Kim
et al., 2001; Kalinina et al., 2006). Thus, a potential role
of catalase during the acquisition of cancer cell resistance
to chemotherapeutic agents was explored by overexpress-
ing the human enzyme in MCF-7 cells, a human derived
breast cancer cell line (Glorieux et al., 2011). No ­particular
resistance against conventional chemotherapies like
doxorubicin, cisplatin and paclitaxel was observed in
­
cells overexpressing catalase but they were more resistant
to the pro-oxidant effect induced by an H2O2-generating
system (Glorieux et al., 2011).
In addition, catalase mitochondria overexpression
in mice enables an increase of lifespan by 20% (Schriner
et  al., 2005). In such animals, the development of mito-
chondrial deletions was reduced and heart disease and
the onset of cataracts were delayed.
Regarding catalase down-regulation, no particular
sensitivity was observed as catalase-deficient mice are
viable and fertile (Ho et al., 2004). They develop normally
with a normal hematological profile, but after trauma the
mitochondria shows defects in the oxidative phosphoryla-
tion. Note that humans may also be deficient in catalase, a
condition known as acatalasemia that is characterized by
a low catalase rate, but it is still rare and usually benign
(Goth et al., 2004).
In this context, there are benign polymorphisms of
the catalase gene for which no change of catalase expres-
sion or activity was detected (Goth et  al., 2004). They
include single nucleotide substitutions in the promoter,
5′ untranslated region, intron 1, exon 1, exon 9 and 10
(Goth et al., 2004). To note that the catalase gene encodes
one single protein of 526 amino acids and the single locus
has been mapped to chromosome 11p13 (Wieacker et al.,
1980). The length of the catalase gene is 34 kb, it contains
12 introns and 13 exons generating a mRNA of 2286 bp
(Quan et al., 1986).
Conversely, some catalase mutations provoke changes
in either catalase expression or activity and may be
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM
1100      C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach

associated with some diseases. For instance, a higher tran- (i.e. loss of heterozygosity) of the catalase gene in non-
scriptional activity in two human cancer cell lines, namely small-cell lung cancer cells (Ludwig et  al., 1991; Fong
HepG2 and K562 cells, was observed in the case of common et al., 1994; Shipman et al., 1998) or deletion of chromo-
functional C-T substitution polymorphism in the promoter some 11p, as has been observed in children affected by
region (−262) of the human catalase gene (­Forsberg et al., Wilms’ tumor, aniridia, gonadoblastoma and retardation
2001) but no mutations have been detected in the coding (WAGR) syndrome (Dufier et al., 1981; Gregoire et al., 1983;
sequence, to our knowledge, in patients suffering from Barletta et al., 1985; Michalopoulos et al., 1985; van Hey-
cancer. Recent studies have focused on the associations ningen et al., 1985).
of catalase polymorphisms with various types of cancer
but many inconsistent results about the relationship
between the catalase gene polymorphism and cancer risk
were reported. Recently, two meta-analyses pointed out a
Regulation of catalase expression
correlation exists between this polymorphism C-262T and in cancer cells
prostate cancer (Liu et al., 2016; Wang et al., 2016).
Different catalase mutations in patients can cause It is generally accepted that the cellular maintenance of
decreased catalase activity leading to increased H2O2 con- redox homeostasis is controlled by a complex network
centrations in the blood and tissues. Table 1 shows the of antioxidant enzymes (i.e. superoxide dismutases and
polymorphism of the catalase gene in patients suffering glutathione peroxidases) whose expression is under the
from hypocatalasemia (about 50% of catalase activities) fine-tuning control of the Keap1-Nrf2  signaling pathway
or acatalasemia (less than 10% of catalase activities). (Menegon et al., 2016). Nevertheless, the molecular mech-
Depending on the mutations, such patients may be anisms regulating the expression of catalase – the oldest
subject to an increased risk of type 2 diabetes, vitiligo and known and first discovered antioxidant enzyme – are
increased blood pressure (Goth et  al., 2004). When the independent of this pathway and not totally elucidated.
mutations are located in exons as in Japanese and Hun- Therefore, the fine-tuning regulation of this enzyme
garian acatalasemia, a truncated or mutated catalase is should be prior elucidated in order to find a new approach
synthetized and functionally less active. Takahara was the to modulate the antioxidant status in cancer cells.
first to describe acatalasemia and this pathology is often Interestingly, despite the existence of diverse protec-
benign but Japanese patients can suffer from oral gan- tion mechanisms against oxidant injuries, a consensus
grenes and esophageal ulcerations (Takahara’s disease), emerged in the scientific literature about an alteration
probably promoted by H2O2 generated by phagocytic cells of redox homeostasis within tumor cells. Indeed, they
and bacterial actions (Takahara, 1952). produce large amounts of ROS that are involved in the
Decreased activity of catalase has also been observed maintenance of genetic instability favoring cancer cell
in various genetic alterations, for example, loss of alleles proliferation. Meanwhile, altered expression levels of
catalase have been reported in cancer tissues as com-
pared to their normal counterparts. Thus, as compared to
Table 1: Catalase gene polymorphisms in patients suffering from
hypocatalasemia or acatalasemia.
normal tissues of the same origin, some authors reported
an increased catalase expression in tumors (Sander
Mutations Position Region Associated disease et  al., 2003; Hwang et  al., 2007; Rainis et  al., 2007),
whereas other studies showed a catalase down-regula-
G insertion Codon 48 Exon 2 Diabetes type 2
T→A Codon 53 Exon 2 Diabetes type 2
tion (Marklund et al., 1982; Baker et al., 1997; Lauer et al.,
G→C Codon 66 Exon 2 Diabetes type 2 1999; Chung-man et  al., 2001; Cullen et  al., 2003; Kwei
C→T −773a Promoter Hypertension et  al., 2004), indicating that cancer cells are frequently
T→C Codon 388 Exon 9 Vitiligo more sensitive to an oxidative stress. For instance, we
G→A 5b Intron 4 Japanese hypocatalasemia (A) have reported an important decrease of catalase activity
T deletion Codon 134 Exon 4 Japanese hypocatalasemia (B)
in different cancer cell lines, as shown in Table 2 (Verrax
GA insertion Codon 67 Exon 2 Hungarian hypocatalasemia (A)
G insertion Codon 58 Exon 2 Hungarian hypocatalasemia (B) et  al., 2009; Beck et  al., 2011a; Glorieux et  al., 2011).
G→T 5b Intron 7 Hungarian hypocatalasemia (C) Briefly, catalase levels can vary after short treatments to
G→A Codon 354 Exon 9 Hungarian hypocatalasemia (D) H2O2 (Rohrdanz and Kahl, 1998; Rohrdanz et al., 2001; Sen
This table was adapted from Goth et al. (2004).
et al., 2003) and catalase expression is modified in cancer
a
Position from the ATG translation start. cell lines rendered resistant to chronic exposures to H2O2
b
Position from the first nucleotide in the intron sequence. (Kasugai and Yamada, 1992; Nenoi et al., 2001) or certain

Brought to you by | Bibliothèques de l'UCL

Authenticated
Download Date | 9/8/17 1:29 PM
 C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach      1101
Table 2: Catalase enzyme activity in cells from diver origins.
Type of cells Normal origin
Mouse hepatocytes 96.45 ± 6.32
Human leukocytes 44.55 ± 1.80
Human mammary epithelial cells 13.14 ± 3.04c
Catalase activity (U/mg proteins) in normal and cancer cell lines. aTLT mouse hepatocarcinoma cells; bK562 human CML cells; c250MK cells;
and dMCF-7 human mammary cells. Data were analyzed by unpaired t-test. ep-Value ≤ 0.01; fp-value ≤ 0.001.
chemotherapeutic compounds such as doxorubicin
(Ramu et  al., 1984; Akman et  al., 1990; Kim et  al., 2001;
Kalinina et  al., 2006). Although mechanisms controlling
catalase expression have been partially elucidated, the
decreased catalase expression in cancer cells still remains
an unanswered question.
The regulation of catalase expression in cancer cells
is a complex process because different levels of regula-
tion are thought to be involved. In a recent review, we
discussed the different mechanisms playing a potential
role in the regulation of its expression in both healthy
and tumor cells (Glorieux et al., 2015). They include tran-
scriptional regulation, represented by the activity of tran-
scription factors that induce or repress the transcriptional
activity of catalase promoters, post-transcriptional regu-
lation (mRNA stability) and post-translational modifica-
tion (phosphorylation and ubiquitination of the protein).
In addition, epigenetic (DNA methylation, modifications
of histones) changes or genetic alterations can also be
involved playing a role in governing proper levels of cata-
lase activity in these cells.
Regarding transcription it should be noted that the
­catalase gene has all the characteristics of a housekeeping
gene (no TATA box, no INR sequence, high GC content in
promoter) and a core promoter which is highly conserved
among species (Quan et al., 1986; Nakashima et al., 1990;
Reimer et  al., 1994). In this core promoter, the presence
of DNA binding sites for transcription factors like NF-Y
and Sp1 has an essential role in the positive regulation of
catalase expression (Nenoi et al., 2001). Additional tran-
scription factors have also been involved in this regulatory
process. In fact, there is strong evidence that the protein
Akt/PKB in the PI3K signaling pathway plays a major role
in the expression of catalase by modulating the activity of
FoxO3a (Turdi et al., 2007; Venkatesan et al., 2007; Akca
et al., 2013). Therefore, targeting PI3K/Akt/mTOR (LoPic-
colo et  al., 2008; Rodon et  al., 2013) may be an efficient
way to increase the expression of catalase in tumors and
inhibit tumor cell growth.
In this last decade, other transcription factors
(PPARγ, Oct-1, etc.) as well as genetic, epigenetic and
post-transcriptional processes are emerging as crucial
Cancer origin References
11.12 ± 4.43a,f Verrax et al. (2009)
16.36 ± 3.60b,e Beck et al. (2011a)
5.44 ± 0.88d,e Glorieux et al. (2016a)
contributors to the negative regulation of catalase expres-
sion (Glorieux et  al., 2015). Specifically, we investigated
the transcriptional regulatory mechanism controlling
catalase expression in human mammary cell lines. To
this end, we have made a human breast MCF-7 cancer
cell line resistant to oxidative stress, the so-called Resox
cells. These cells show decreased ROS basal levels and an
increased activity of some antioxidant enzymes, notably
catalase (Dejeans et al., 2012; Glorieux et al., 2015, 2016b).
A novel promoter region, responsible for the regulation of
catalase expression, was identified at −1518/−1226 locus
in Resox cells (Glorieux et  al., 2016a). The AP-1 family
member JunB and retinoic acid receptor alpha (RARα)
mediate catalase transcriptional activation and repres-
sion, respectively, by controlling chromatin remodeling
through a histone deacetylases-dependent mechanism
(Glorieux et  al., 2016a). Indeed, RARα and JunB act in
collaboration with transcription factors or other proteins
on either a closed- or an open-promoter chromatin status
regulating the expression of catalase in breast cancer
cells (Figure 2). Thus, cancer adaptation to oxidative
stress, regulated by transcriptional factors through chro-
matin remodeling appears as a new mechanism to target
cancer cells.
Oxidative stress-based therapies
against cancer
As previously mentioned, cancer cells are generally defi-
cient in antioxidant enzymes, thus, any increase in ROS
levels would be a menace to the precarious redox balance
of cancer cells making them vulnerable to an additional
oxidative stress. Given that weakness, the loss of redox
homeostasis represents an interesting target for research
and development of new molecules with antitumor activ-
ity and numerous drugs are currently being clinically eval-
uated. Therefore, several strategies have been developed
looking for the disruption of tumor cell redox homeostasis
and a subsequent cancer cell death (Demizu et al., 2008;
Trachootham et al., 2009; Verrax et al., 2009).
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM
1102      C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach
Figure 2: Hypothetical mechanism of catalase regulation in breast
cancer cell lines.
A human breast MCF-7 cancer cell line resistant to oxidative stress
was generated (Resox cells) by chronically exposing MCF-7 cells with
an H2O2-generating system (Dejeans et al., 2012). These cells show
increased expression of catalase. A novel promoter region, respon-
sible for the regulation of catalase expression, was identified at
−1518/−1226 locus in Resox cells (Glorieux et al., 2016a). The AP-1
family member JunB and retinoic acid receptor alpha (RARα) mediate
catalase transcriptional activation and repression, respectively, by
controlling chromatin remodeling through a histone deacetylases
(HDAC)-dependent mechanism. (HAT: Histobe acetyltransferase).
Adapted from Glorieux et al. (2016a).
One of these strategies is the use of ROS-generating
compounds such as arsenic trioxide (ATO), currently
employed against promyelocytic leukemia (Valenzuela
et al., 2014; Lo-Coco et al., 2016), or doxorubicin, an anthra-
cycline used for the treatment of several types of cancer
(i.e. breast cancer). Indeed, the impairment of mitochon-
drial function due to increased levels of superoxide anion
Figure 3: The quinone redox cycling hypothesis.
The biological activity showed by menadione mainly relies upon its ability to accept one electron from ascorbate to form a semiquinone
radical. When the semiquinone is reduced back to its quinone form, superoxide anion is produced which by dismutation generates hydro-
gen peroxide.
is supposed to be the main mechanism of both chemo-
therapeutic drugs (Thayer, 1977; Pelicano et al., 2003). A
decrease in antioxidant levels has also been proposed.
For instance, glutathione (GSH) levels may be decreased
either by its direct binding with phenylethylisothiocy-
anate (PEITC) and sulphoraphane (Trachootham et  al.,
2009) or by inhibition of γ-glutamylcysteine synthetase
activity (a key enzyme involved in GSH synthesis) as done
by Buthionine sulfoximine (Griffith and Meister, 1979).
The development of specific inhibitors of thioredoxin and
thioredoxin reductases was also carried out. Inhibitors
of thioredoxin, such as PX-12, were shown to have potent
antitumor activities (Welsh et al., 2003; Baker et al., 2006).
Conversely, the overexpression of Trx1 is correlated with
resistance to anti-cancer drugs (Baker et al., 2006; Kaimul
et al. 2007).
As quinones display redox cycling abilities thus gen-
erating ROS (Kappus and Sies, 1981), the association of
menadione (a naphthoquinone derivative) and ascor-
bate (Figure 3), was employed to trigger tumor cell death
(Verrax et al., 2011b). This association (Asc/Men) has been
shown to have potent in vitro and in vivo antitumor activi-
ties enhancing as well the therapeutic effect of currently
used anticancer drugs (Taper et  al., 1987; Buc C ­ alderon
et  al., 2002; Verrax et  al., 2003). We hypothesized that
H2O2, issued from the redox cycling, is the oxidant species
responsible for antitumor effects observed both in vitro
and in vivo (Verrax et  al., 2006, 2007; Verrax and Buc
Calderon, 2009). The induced oxidative stress provokes
cell necrosis by a wide variety of processes including
ATP depletion (Verrax et  al., 2004, 2005, 2011a), disrup-
tion of Ca2+ homeostasis (Dejeans et al., 2010) and loss of
HSP90 chaperone activity (Beck et al., 2009, 2011b, 2012).
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM
 C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach      1103
Figure 4: Arsenic trioxide (ATO) decreases catalase expression in
breast cancer cells and sensitizes them to pro-oxidant drugs.
Based on the vulnerability of tumor cells to an oxidative
stress, we have induced the alteration of their intracellu-
lar redox homeostasis as a new strategy in the research
and development of new antitumor drugs (Benites et al.,
2010; Arenas et  al., 2013; Valderrama et  al., 2015). A
similar approach has been recently developed by using
the SnFe2O4 nanocrystals, a heterogeneous Fenton cata-
lyst, which once internalized into the cancer cells, convert
H2O2 into hydroxyl radicals inducing apoptotic cell death.
In normal cells, the oxidative injury induced by SnFe2O4 is
prevented by catalase (Lee et al., 2017).
As ATO increases the levels of ROS (Valenzuela et al.,
2014) and Asc/Men increases the cytotoxicity of chemo-
therapeutic drugs (Taper et al., 1987), we formulated the
following hypothesis: Asc/Men potentiates ATO-mediated
cytotoxicity (Figure 4). ATO decreases catalase expression
most likely by activating Akt pathway and/or inducing
RARα, meanwhile Asc/Men generates H2O2. Despite that
Resox cells display high antioxidant defenses (Dejeans
et al., 2012; Glorieux et al., 2015, 2016b), an enhanced cell
death was observed when they were exposed to a mixture
containing sublethal doses of Asc/Men and ATO. This is
likely due to a decreased transcriptional activity of the
human catalase −1518/+16 promoter caused by ATO result-
ing in less catalase protein (Glorieux et al., 2017, unpub-
lished results).
Conclusions
Under stress conditions, the antioxidant enzyme catalase
plays a major role by detoxifying H2O2. As consequences,
a change of its activity or expression will lead to patho-
logical processes as Zellweger syndrome, acatalasemia or
WAGR syndrome. The subcellular localization of catalase
is mainly peroxisomal but a shuttle between this organelle
and cytoplasm exists and may be involved in the protec-
tion of key cellular elements (i.e. proteins, chromosomes)
against an oxidative damage.
Our group and others demonstrated that catalase
expression is also altered in cancer cells, most likely to
favor cell proliferation by inducing genetic instability
and activation of oncogenes. The regulation of catalase
expression appears to be mainly controlled at transcrip-
tional levels although other mechanisms may also be
involved. In addition of transcription factors like Sp1 and
NF-Y, JunB and RARα transcription factors are crucial
regulators in breast cancer cells by recruiting proteins
involved in transcriptional complexes and chromatin
remodeling.
Therefore, catalase can be a future therapeutic target
in the context of cancer by using pro-oxidant approaches.
Acknowledgments: The authors thank Professor Helmut
Sies for the splendid discussion and his precious input.
This project was funded by FNRS-Televie Grant (grant n°
7.4575.12F).
References
Akca, H., Demiray, A., Aslan, M., Acikbas, I., and Tokgun, O. (2013).
Tumour suppressor PTEN enhanced enzyme activity of GPx,
SOD and catalase by suppression of PI3K/AKT pathway in non-
small cell lung cancer cell lines. J. Enzyme Inhib. Med. Chem.
28, 539–544.
Akman, S.A., Forrest, G., Chu, F.F., Esworthy, R.S., and Doroshow,
J.H. (1990). Antioxidant and xenobiotic-metabolizing enzyme
gene expression in doxorubicin-resistant MCF-7 breast cancer
cells. Cancer Res. 50, 1397–1402.
Arenas, P., Pena, A., Rios, D., Benites, J., Muccioli, G.G., Buc Calde-
ron, P., and Valderrama, J.A. (2013). Echo-friendly synthesis
and antiproliferative evaluation of oxygen substituted diaryl
ketones. Molecules 18, 9818–9832.
Baker, A.M., Oberley, L.W., and Cohen, M.B. (1997). Expression of
antioxidant enzymes in human prostatic adenocarcinoma.
Prostate 32, 229–233.
Baker, A.F., Dragovich, T., Tate, W.R., Ramanathan, R.K., Roe, D.,
Hsu, C.H., Kirkpatrick, D.L., and Powis, G. (2006). The antitu-
mor thioredoxin-1 inhibitor PX-12 (1-methylpropyl 2-imidazolyl
disulfide) decreases thioredoxin-1 and VEGF levels in cancer
patient plasma. J Lab Clin Med. 147, 83–90.
Barletta, C., Castello, M.A., Ferrante, E., Mavelli, I., Clerico, A.,
­Ciriolo, M.R., and Vignetti, P. (1985). 11p13 deletion and
reduced RBC catalase in a patient with aniridia, glaucoma and
bilateral Wilms’ tumor. Tumori 71, 119–121.
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM
1104      C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach
Bauer, G. (2012). Tumor cell-protective catalase as a novel target for
rational therapeutic approaches based on specific intercellular
ROS signaling. Anticancer Res. 32, 2599–2624.
Bauer, G. (2015). Increasing the endogenous NO level causes
catalase inactivation and reactivation of intercellular apoptosis
signaling specifically in tumor cells. Redox Biol. 6, 353–371.
Bauer, G. and Graves, D.B. (2016). Mechanisms of selective
antitumor action of cold atmospheric plasma-derived reac-
tive oxygen and nitrogen species. Plasma Process Polym. 13,
1157–1178.
Bauer, G. and Motz, M. (2016). The antitumor effect of single-
domain antibodies directed towards membrane-associated
catalase and superoxide dismutase. Anticancer Res. 36,
5945–5956.
Beck, R., Verrax, J., Gonze, T., Zappone, M., Curi Pedrosa, R., Taper,
H., Feron, O., and Buc Calderon, P. (2009). Hsp90 cleavage by
an oxidative stress leads to Bcr-Abl degradation and leukemia
cell death. Biochem. Pharmacol. 77, 375–383.
Beck, R., Pedrosa, R.C., Dejeans, N., Glorieux, C., Leveque, P., Gal-
lez, B., Taper, H., Eeckhoudt, S., Knoops, L., Buc Calderon, P.,
et al. (2011a). Ascorbate/menadione-induced oxidative stress
kills cancer cells that express normal or mutated forms of the
oncogenic protein Bcr-Abl. An in vitro and in vivo mechanistic
study. Invest New Drugs 29, 891–900.
Beck, R., Dejeans, N., Glorieux, C., Curi Pedrosa, R., Vasquez, D.,
Valderrama, J.A., Buc Calderon, P., and Verrax, J. (2011b). Mole-
cular chaperone Hsp90 as a target for oxidant-based anticancer
therapies. Curr. Med. Chem. 18, 2816–2825.
Beck, R., Dejeans, N., Glorieux, C., Creton, M., Delaive, E., Dieu, M.,
Raes, M., Leveque, P., Gallez, B., Depuydt, M., et al. (2012).
Hsp90 is cleaved by reactive oxygen species at a highly con-
served N-terminal amino acid motif. PLoS One 7, e40795.
Benites, J., Valderrama, J.A., Bettega, K., Curi Pedrosa, R., Buc
Calderon, P., and Verrax, J. (2010). Biological evaluation of
donor-acceptor aminonaphthoquinones as antitumor agents.
Eur. J. Med. Chem. 45, 6052–6057.
Böhm, B., Heinzelmann, S., Motz, M., and Bauer, G. (2015). Extracel-
lular localization of catalase is associated with the transformed
state of malignant cells. Biol Chem. 396, 1339–1356.
Brown, G.C. (1995). Reversible binding and inhibition of catalase by
nitric oxide. Eur J Biochem. 232, 188–191.
Brunelli, L., Yermilov, V., and Beckman, J.S. (2001). Modulation of
catalase peroxidatic and catalatic activity by nitric oxide. Free
Radic. Biol. Med. 30, 709–714.
Buc Calderon, P., Cadrobbi, J., Marquez, C., Hong-Ngo, N., Jamison,
J.M., Gilloteaux, J., Summers, J.L., and Taper, H.S. (2002).
Potential therapeutic application of the association of vitamins
C and K3 in cancer treatment. Curr. Med. Chem. 9, 2271–2285.
Chance, B. (1948). The enzyme-substrate compounds of catalase
and peroxides. Nature 161, 914–917.
Chance, B. (1949). The primary and secondary compounds of
catalase and methyl or ethyl hydrogen peroxide; kinetics and
activity. J. Biol. Chem. 179, 1341–1369.
Chance, B., Greenstein, D.S., and Roughton, F.J. (1952). The
mechanism of catalase action. I. Steady-state analysis. Arch.
Biochem. Biophys. 37, 301–321.
Chance, B., Sies, H., and Boveris, A. (1979). Hydroperoxide meta-
bolism in mammalian organs. Physiol Rev. 59, 527–605.
Chung-man, H.J., Zheng, S., Comhair, S.A., Farver, C., and Erzurum,
S.C. (2001). Differential expression of manganese ­superoxide
dismutase and catalase in lung cancer. Cancer Res. 61,
8578–8585.
Cullen, J.J., Mitros, F.A., and Oberley, L.W. (2003). Expression of anti-
oxidant enzymes in diseases of the human pancreas: another
link between chronic pancreatitis and pancreatic cancer.
Pancreas 26, 23–27.
Deichman, G.I. (2000). Natural selection and early changes of
phenotype of tumor cells in vivo: acquisition of new defense
mechanisms. Biochemistry (Mosc). 65, 78–94.
Deichman, G.I. (2002). Early phenotypic changes of in vitro trans-
formed cells during in vivo progression: possible role of the
host innate immunity. Semin. Cancer Biol. 12, 317–326.
Dejeans, N., Tajeddine, N., Beck, R., Verrax, J., Taper, H., Gailly, P.,
and Buc Calderon, P. (2010). Endoplasmic reticulum calcium
release potentiates the ER stress and cell death caused by
an oxidative stress in MCF-7 cells. Biochem. Pharmacol. 79,
1221–1230.
Dejeans, N., Guenin, S., Glorieux, C., Beck, R., Sid, B., Rousseau, R.,
Bisig, B., Delvenne, P., Buc Calderon, P., and Verrax, J. (2012).
Overexpression of GRP94 in breast cancer cells resistant to oxi-
dative stress promotes high levels of cancer cell proliferation
and migration: implications for tumor recurrence. Free Radic.
Biol. Med. 52, 993–1002.
Demizu, Y., Sasaki, R., Trachootham, D., Pelicano, H., Colacino, J.A.,
Liu, J., and Huang, P. (2008). Alterations of cellular redox state
during NNK-induced malignant transformation and resistance
to radiation. Antiox. Redox Signal. 10, 951–961.
Dufier, J.L., Phug, L.H., Schmelck, P., Fekete, C., de Grouchy, G.J.,
Turleau, C., and Haye, C. (1981). [Intercalary deletion of the
short arm of chromosome 11: aniridia, glaucoma, staturopon-
deral and mental retardation, sexual ambiguity, gonadoblas-
toma and catalase deficiency]. Bull. Soc. Ophtalmol. Fr. 81,
747–749.
Fenton, H.J.H. (1894). Oxidation of tartaric acid in presence of iron. J.
Chem. Soc. Trans. 65, 899–911.
Fita, I. and Rossmann, M.G. (1985a). The NADPH binding site on beef
liver catalase. Proc. Natl. Acad. Sci. USA 82, 1604–1608.
Fita, I. and Rossmann, M.G. (1985b). The active center of catalase. J.
Mol. Biol. 185, 21–37.
Fong, K.M., Zimmerman, P.V., and Smith, P.J. (1994). Correlation
of loss of heterozygosity at 11p with tumour progression and
survival in non-small cell lung cancer. Genes Chromosomes
Cancer 10, 183–189.
Forsberg, L., Lyrenas, L., de Faire, U., and Morgenstern, R. (2001).
A common functional C-T substitution polymorphism in the
promoter region of the human catalase gene influences
transcription factor binding, reporter gene transcription and is
correlated to blood catalase levels. Free Radic. Biol. Med. 30,
500–505.
Gabdoulline, R.R., Kummer, U., Olsen, L.F., and Wade, R.C. (2003).
Concerted simulations reveal how peroxidase compound
III formation results in cellular oscillations. Biophys. J. 85,
1421–1428.
Gebicka, L. and Didik, J. (2009). Catalytic scavenging of peroxyni-
trite by catalase. J. Inorg. Biochem. 103, 1375–1379.
Glorieux, C., Dejeans, N., Sid, B., Beck, R., Buc Calderon, P.,
and Verrax, J. (2011). Catalase overexpression in mammary
cancer cells leads to a less aggressive phenotype and an
altered response to chemotherapy. Biochem. Pharmacol. 82,
1384–1390.
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM
 C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach      1105
Glorieux, C., Zamocky, M., Sandoval, C.J.M., Verrax, J., and Buc Cal-
deron, P. (2015). Regulation of catalase expression in healthy
and cancer cells. Free Radic. Biol. Med. 87, 84–97.
Glorieux, C., Sandoval, J.M., Fattaccioli, A., Dejeans, N., Garbe, J.C.,
Dieu, M., Verrax, J., Renard, P., Huang, P., and Buc Calderon, P.
(2016a). Chromatin remodeling regulates catalase expression
during cancer cells adaptation to chronic oxidative stress. Free
Radic. Biol. Med. 99, 436–450.
Glorieux, C., Sandoval, J.M., Dejeans, N., Ameye, G., Poirel, H.A.,
Verrax, J., and Buc Calderon P. (2016b). Overexpression of
NAD(P)H:quinone oxidoreductase 1 (NQO1) and genomic gain
of the NQO1 locus modulates breast cancer cell sensitivity to
quinones. Life Sci. 145, 57–65.
Goth, L., Rass, P., and Pay, A. (2004). Catalase enzyme mutations
and their association with diseases. Mol. Diagn. 8, 141–149.
Gregoire, M.J., Pernot, C., Himont, F., Pierson, M., and Gilgenkrantz,
S. (1983). [Chromosome 11 and cancer]. J.Genet.Hum. 31,
31–36.
Griffith, O.W. and Meister, A. (1979). Potent and specific inhibition
of glutathione synthesis by buthionine sulfoximine (S-n-butyl
homocysteine sulfoximine). J. Biol. Chem. 254, 7558–7560.
Heinzelmann, S. and Bauer, G. (2010). Multiple protective functions
of catalase against intercellular apoptosis-inducing ROS signal-
ling of human tumor cells, Biol. Chem. 391, 675–693.
Ho, Y.S., Xiong, Y., Ma, W., Spector, A., and Ho, D.S. (2004). Mice
lacking catalase develop normally but show differential sensi-
tivity to oxidant tissue injury. J. Biol. Chem. 279, 32804–32812.
Hwang, T.S., Choi, H.K., and Han, H.S. (2007). Differential expres-
sion of manganese superoxide dismutase, copper/zinc super-
oxide dismutase, and catalase in gastric adenocarcinoma and
normal gastric mucosa. Eur. J. Surg. Oncol. 33, 474–479.
Johansson, L.H. and Borg, L.A. (1988). A spectrophotometric method
for determination of catalase activity in small tissue samples,
Anal. Biochem. 174, 331–336.
Jones, P. and Dunford, H.B. (2005). The mechanism of Compound I
formation revisited. J. Inorg. Biochem. 99, 2292–2298.
Kaimul, A.M., Nakamura, H., Masutani, H., and Yodoi, J. (2007).
Thioredoxin and thioredoxin-binding protein-2 in cancer and
metabolic syndrome. Free Radic. Biol. Med. 43, 861–868.
Kalinina, E.V., Chernov, N.N., Saprin, A.N., Kotova, Y.N., Andreev,
Y.A., Solomka, V.S., and Scherbak, N.P. (2006). Changes in
expression of genes encoding antioxidant enzymes, heme
oxygenase-1, Bcl-2, and Bcl-xl and in level of reactive oxygen
species in tumor cells resistant to doxorubicin. Biochemistry
(Mosc.) 71, 1200–1206.
Kappus, H. and Sies, H. (1981). Toxic drug effects associated with
oxygen metabolism: redox cycling and lipid peroxidation. Expe-
rientia 37, 1233–1241.
Kasugai, I. and Yamada, M. (1992). High production of catalase in
hydrogen peroxide-resistant human leukemia HL-60 cell lines.
Leuk. Res. 16, 173–179.
Kato, S., Ueno, T., Fukuzumi, S., and Watanabe, Y. (2004). Catalase
reaction by myoglobin mutants and native catalase: mechanis-
tic investigation by kinetic isotope effect. J. Biol. Chem. 279,
52376–52381.
Keilin, D. and Hartree, E.F. (1945). Properties of catalase. Catalysis of
coupled oxidation of alcohols. Biochem. J. 39, 293–301.
Kim, H.S., Lee, T.B., and Choi, C.H. (2001). Down-regulation of cata-
lase gene expression in the doxorubicin-resistant AML subline
AML-2/DX100. Biochem. Biophys. Res. Commun. 281, 109–114.
Kirkman, H.N. and Gaetani G.F. (1984). Catalase: a tetrameric
enzyme with four tightly bound molecules of NADPH. Proc.Natl.
Acad. Sci. USA 81, 4343–4347.
Kirkman, H.N., Rolfo, M., Ferraris, A.M., and Gaetani, G.F. (1999).
Mechanisms of protection of catalase by NADPH. Kinetics and
stoichiometry. J. Biol. Chem. 274, 13908–13914.
Koepke, J.I., Nakrieko, K.A., Wood, C.S., Boucher, K.K., Terlecky, L.J.,
Walton, P.A., and Terlecky, S.R. (2007). Restoration of peroxiso-
mal catalase import in a model of human cellular aging. Traffic
8, 1590–1600.
Kwei, K.A., Finch, J.S., Thompson, E.J., and Bowden, G.T. (2004).
Transcriptional repression of catalase in mouse skin tumor
progression. Neoplasia 6, 440–448.
Lauer, C., Volkl, A., Riedl, S., Fahimi, H.D., and Beier, K. (1999).
Impairment of peroxisomal biogenesis in human colon carci-
noma. Carcinogenesis 20, 985–989.
Lazarow, P.B. and De Duve, C. (1973). The synthesis and turnover
of rat liver peroxisomes. V. Intracellular pathway of catalase
synthesis. J. Cell Biol. 59, 507–524.
Lee, K.T., Lu, Y.J., Mi, F.L., Burnouf, T., Wei, Y.T., Chiu, S.C., Chuang,
E.Y., and Lu, S.Y. (2017). Catalase-modulated heterogeneous
Fenton reaction for selective cancer cell eradication: SnFe2O4
nanocrystals as an effective reagent for treating lung cancer
cells. ACS Appl. Mater. Interfaces 9, 1273–1279.
Liu, K., Liu, X., Wang, M., Wang, X., Kang, H., Lin, S., Yang, P., Dai,
C., Xu, P., Li, S., et al. (2016). Two common functional catalase
gene polymorphisms (rs1001179 and rs794316) and cancer
susceptibility: evidence from 14,942 cancer cases and 43,285
controls. Oncotarget 7, 62954–62965.
Lo-Coco, F., Cicconi, L., and Breccia, M. (2016). Current standard
treatment of adult acute promyelocytic leukaemia. Br. J. Hae-
matol. 172, 841–854.
Loew, O. (1900). A new enzyme of general occurrence in organisms.
Science 11, 701–702.
LoPiccolo, J., Blumenthal, G.M., Bernstein, W.B., and Dennis, P.A.
(2008). Targeting the PI3K/Akt/mTOR pathway: effective
combinations and clinical considerations. Drug Resist. Updat.
11, 32–50.
Ludwig, C.U., Raefle, G., Dalquen, P., Stulz, P., Stahel, R., and
Obrecht, J.P. (1991). Allelic loss on the short arm of chro-
mosome 11 in non-small-cell lung cancer. Int. J. Cancer 49,
661–665.
Marklund, S.L., Westman, N.G., Lundgren, E., and Roos, G.
(1982). Copper- and zinc-containing superoxide dismutase,
manganese-containing superoxide dismutase, catalase, and
glutathione peroxidase in normal and neoplastic human cell
lines and normal human tissues. Cancer Res. 42, 1955–1961.
Matsui, T., Ozaki, S., Liong, E., Phillips, G.N., and Watanabe, Jr., Y.
(1999). Effects of the location of distal histidine in the reac-
tion of myoglobin with hydrogen peroxide. J. Biol. Chem. 274,
2838–2844.
Menegon, S., Columbano, A., and Giordano, S. (2016). The dual
roles of Nrf2 in cancer. Trends Mol. Med. 22, 578–593.
Michalopoulos, E.E., Bevilacqua, P.J., Stokoe, N., Powers, V.E., Wil-
lard, H.F., and Lewis, W.H. (1985). Molecular analysis of gene
deletion in aniridia-Wilms tumor association. Hum. Genet. 70,
157–162.
Middelkoop, E., Wiemer, E.A., Schoenmaker, D.E., Strijland, A., and
Tager, J.M. (1993). Topology of catalase assembly in human
skin fibroblasts. Biochim. Biophys. Acta 1220, 15–20.
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM
1106      C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach
Moran, E.C., Kamiguti, A.S., Cawley, J.C., and Pettitt, A.R. (2002).
Cytoprotective antioxidant activity of serum albumin and
autocrine catalase in chronic lymphocytic leukaemia. Br. J. Hae-
matol. 116, 316–328.
Mueller, S., Riedel, H.D., and Stremmel, W. (1997). Direct evidence
for catalase as the predominant H2O2 -removing enzyme in
human erythrocytes. Blood 90, 4973–4978.
Murakami, K., Ichinohe, Y., Koike, M., Sasaoka, N., Iemura, S., Nat-
sume, T., and Kakizuka, A. (2013). VCP is an integral component
of a novel feedback mechanism that controls intracellular
localization of catalase and H2O2 Levels. PLoS One 8, e56012.
Nagem, R.A., Martins, E.A., Goncalves, V.M., Aparicio, R., and
Polikarpov, I. (1999). Crystallization and preliminary X-ray
diffraction studies of human catalase. Acta Crystallogr. D Biol.
Crystallogr. 55, 1614–1615.
Nakashima, H., Yamamoto, M., Goto, K., Osumi, T., Hashimoto, T.,
and Endo, H. (1990). Isolation and characterization of the rat
catalase-encoding gene. Gene 89, 295.
Nakatani, M. (1961). Studies on histidine residues in hemeproteins
related to their activities. V. Photooxidation of catalase in the
presence of methylene blue. J. Biochem. 49, 98–102.
Nenoi, N., Ichimura, S., Mita, K., Yukawa,O., and Cartwright, I.L.
(2001). Regulation of the catalase gene promoter by Sp1,
CCAAT-recognizing factors, and a WT1/Egr-related factor in
hydrogen peroxide-resistant HP100 cells. Cancer Res. 61,
5885–5894.
Oshino, N., Oshino, R., and Chance, B. (1973). The characteristics
of the ‘peroxidatic’ reaction of catalase in ethanol oxidation.
Biochem J. 131, 555–563.
Otera, H. and Fujiki, Y. (2012). Pex5p imports folded tetrameric cata-
lase by interaction with Pex13p. Traffic 13, 1364–1377.
Park, Y.S., You, S.Y., Cho, S., Jeon, H.J., Lee, S., Cho, D.H., Kim,
J.S., and Oh, J.S. (2016). Eccentric localization of catalase to
protect chromosomes from oxidative damages during meiotic
maturation in mouse oocytes. Histochem. Cell Biol. 146,
281–288.
Pelicano, H., Feng, L., Zhou, Y., Carew, J.S., Hileman, E.O.,
Plunkett, W., Keating, M.J., and Huang, P. (2003). Inhibition
of mitochondrial respiration: a novel strategy to enhance
drug-induced apoptosis in human leukemia cells by a reactive
oxygen species-mediated mechanism. J. Biol. Chem. 278,
37832–37839.
Purdue, P.E. and Lazarow, P.B. (1996). Targeting of human catalase
to peroxisomes is dependent upon a novel COOH-terminal
peroxisomal targeting sequence. J. Cell Biol. 134, 849–862.
Putnam, C.D., Arvai, A.S., Bourne, Y., and Tainer, J.A. (2000). Active
and inhibited human catalase structures: ligand and NADPH
binding and catalytic mechanism. J. Mol. Biol. 296, 295–309.
Quan, F., Korneluk, R.G., Tropak, M.B., and Gravel, R.A. (1986).
Isolation and characterization of the human catalase gene.
Nucleic Acids Res. 14, 5321–5335.
Radi, R., Turrens, J.F., Chang, L.Y., Bush, K.M., Crapo, J.D., and Free-
man, B.A. (1991). Detection of catalase in rat heart mitochon-
dria. J. Biol. Chem. 266, 22028–22034.
Rainis, T., Maor, I., Lanir, A., Shnizer, S., and Lavy, A. (2007).
Enhanced oxidative stress and leucocyte activation in neoplas-
tic tissues of the colon. Dig. Dis. Sci. 52, 526–530.
Ramu, A., Cohen, L., and Glaubiger, D. (1984). Oxygen radical
detoxification enzymes in doxorubicin-sensitive and -resistant
P388 murine leukemia cells. Cancer Res. 44, 1976–1980.
Reimer, D.L., Bailley, J., and Singh, S.M. (1994). Complete cDNA and
5′ genomic sequences and multilevel regulation of the mouse
catalase gene. Genomics 21, 325–336.
Rodon, J., Dienstmann, R., Serra, V., and Tabernero, J. (2013). Devel-
opment of PI3K inhibitors: lessons learned from early clinical
trials. Nat. Rev. Clin. Oncol. 10, 143–153.
Rohrdanz, E. and Kahl, R. (1998). Alterations of antioxidant enzyme
expression in response to hydrogen peroxide. Free Radic. Biol.
Med. 24, 27–38.
Rohrdanz, E., Schmuck, G., Ohler, S., and Kahl, R. (2001). The influ-
ence of oxidative stress on catalase and MnSOD gene transcrip-
tion in astrocytes. Brain Res. 900, 128–136.
Rovira, C. (2005). Structure, protonation state and dynamics of cata-
lase compound II. Chemphyschem. 6, 1820–1826.
Riethmüller, M., Burger. N., and Bauer, G. (2015). Singlet oxygen
treatment of tumor cells triggers extracellular singlet oxygen
generation, catalase inactivation and reactivation of intercellu-
lar apoptosis-inducing signaling. Redox Biol. 6, 157–168.
Sander, C.S., Hamm, F., Elsner, P., and Thiele, J.J. (2003). Oxidative
stress in malignant melanoma and non-melanoma skin cancer.
Br. J. Dermatol. 148, 913–922.
Sandstrom, P.A. and Buttke, P.M. (1993). Autocrine production of
extracellular catalase prevents apoptosis of the human CEM
T-cell line in serum-free medium. Proc. Natl. Acad. Sci. USA 90,
4708–4712.
Scheit, K. and Bauer, G. (2015). Direct and indirect inactivation of
tumor cell protective catalase by salicylic acid and anthocya-
nidins reactivates intercellular ROS signaling and allows for
synergistic effects. Carcinogenesis 36, 400–411.
Schönbein, C.F. (1863). Chemische Mittheilungen. Med. Chir. Trans.
89, 1–38.
Schriner, S.E., Linford, N.J., Martin, G.M., Treuting, P., Ogburn, C.E.,
Emond, M., Coskun, P.E., Ladiges, W., Wolf, N., Van Remmen,
H., et al. (2005). Extension of murine life span by overex-
pression of catalase targeted to mitochondria. Science 308,
1909–1911.
Sen, P., Mukherjee, S., Bhaumik, G., Das, P., Ganguly, S., Choud-
hury, N., and Raha, S. (2003). Enhancement of catalase activity
by repetitive low-grade H2O2 exposures protects fibroblasts
from subsequent stress-induced apoptosis. Mutat. Res. 529,
87–94.
Shimozawa, N., Zhang, Z., Suzuki, Y., Imamura, A., Tsukamoto, T.,
Osumi, T., Fujiki, Y., Orii, T., Barth, P.G., Wanders, R.J., et al.
(1999). Functional heterogeneity of C-terminal peroxisome tar-
geting signal 1 in PEX5-defective patients. Biochem. Biophys.
Res. Commun. 262, 504–508.
Shipman, R., Schraml, P., Colombi, M., and Ludwig, C.U. (1998).
Allelic deletion at chromosome 11p13 defines a tumour sup-
pressor region between the catalase gene and D11S935 in
human non-small cell lung carcinoma. Int. J. Oncol. 12, 107–111.
Sies, H. (1974). Biochemistry of the peroxisome in the liver cell.
Angew. Chem. Int. Ed. Engl. 13, 706–718.
Sies, H. (2017). Hydrogen peroxide as a central redox signaling
molecule in physiological oxidative stress: oxidative eustress.
Redox Biol. 11, 613–619.
Sies, H. and Chance, B. (1970). The steady state level of catalase
compound I in isolated hemoglobin-free perfused rat liver.
FEBS Lett. 11, 172–176.
Stern, K.G. (1937). Spectroscopy of catalase. J. Gen. Physiol. 20,
631–648.
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM
 C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach      1107
Sumner, J.B. and Dounce, A.L. (1937). Crystalline catalase. Science
85, 366–367.
Takahara, S. (1952). Progressive oral gangrene probably due to lack
of catalase in the blood (acatalasaemia); report of nine cases.
Lancet 2, 1101–1104.
Taper, H.S., de Gerlache, J., Lans, M., and Roberfroid, M. (1987).
Non-toxic potentiation of cancer chemotherapy by combined C
and K3 vitamin pre-treatment. Int. J. Cancer 40, 575–579.
Thayer, W.S. (1977). Adriamycin stimulated superoxide formation in
submitochondrial particles. Chem. Biol. Interact. 19, 265–278.
Thénard, L.J. (1811). Observations sur des nouvelles combinaisons
entre l’oxigène et divers acides. Ann. Chim. Phys. 8, 306–312.
Thurman, R.G., Ley, H.G., and Scholz, R. (1972). Hepatic microsomal
ethanol oxidation. Hydrogen peroxide formation and the role of
catalase. Eur. J. Biochem. 25, 420–430.
Trachootham, D., Alexandre, J., and Huang, P. (2009). Targeting can-
cer cells by ROS-mediated mechanisms: a radical therapeutic
approach? Nat. Rev. Drug Discov. 8, 579–591.
Turdi, S., Li, Q., Lopez, F.L., and Ren, J. (2007). Catalase alleviates
cardiomyocyte dysfunction in diabetes: role of Akt, Forkhead
transcriptional factor and silent information regulator 2. Life
Sci. 81, 895–905.
Valderrama, J.A., Rios, D., Muccioli, G.G., Buc Calderon, P., Brito,
I., and Benites, J. (2015). Hetero-annulation reaction between
2-acylnaphthoquinones and 2-aminobenzothiazoles. A new
synthetic route to antiproliferative benzo[g]benzothiazolo[2,3-
b]quinazoline-7,12-quinones. Tetrahedron Lett. 56, 5103–5105.
Valenzuela, M., Glorieux, C., Stokis, J., Sid, B., Sandoval, M., Felipe,
K.B., Kviecinski, M., Verrax, J., and Buc Calderon, P. (2014).
Retinoic acid synergizes ATO-mediated cytotoxicity by preclud-
ing Nrf2 activity in AML cells. Br. J. Cancer 111, 874–882.
van Heyningen, V., Boyd, P.A., Seawright, A., Fletcher, J.M., Fantes,
J.A., Buckton, K.E., Spowart, G., Porteous, D.J., Hill, R.E., and
Newton. M.S. (1985). Molecular analysis of chromosome 11
deletions in aniridia-Wilms tumor syndrome. Proc. Natl. Acad.
Sci. USA 82, 8592–8596.
Venkatesan, B., Mahimainathan, L., Das, F., Ghosh-Choudhury, N.,
and Ghosh, C.G. (2007). Downregulation of catalase by reactive
oxygen species via PI 3 kinase/Akt signaling in mesangial cells.
J. Cell Physiol. 211, 457–467.
Verrax, J. and Buc Calderon, P. (2009). Pharmacologic concentra-
tions of ascorbate are achieved by parenteral administration
and exhibit antitumoral effects. Free Radic. Biol. Med. 47,
32–40.
Verrax, J., Cadrobbi, J., Delvaux, M., Jamison, J.M., Gilloteaux, J.,
Summers, J.L., Taper, H.S., and Buc Calderon, P. (2003). The
association of vitamins C and K3 kills cancer cells mainly by
autoschizis, a novel form of cell death. Basis for their potential
use as coadjuvants in anticancer therapy. Eur. J. Med. Chem.
38, 451–457.
Verrax, J., Cadrobbi, J., Marques, C., Taper, H., Habraken, Y., Piette,
J., and Buc Calderon, P. (2004). Ascorbate potentiates the cyto-
toxicity of menadione leading to an oxidative stress that kills
cancer cells by a non-apoptotic caspase-3 independent form of
cell death. Apoptosis 9, 223–233.
Verrax, J., Delvaux, M., Beghein, N., Taper, H., Gallez, B., and Buc
Calderon, P. (2005). Enhancement of quinone redox cycling
by ascorbate induces a caspase-3 independent cell death in
human leukaemia cells. An in vitro comparative study. Free
Radic. Res. 39, 649–657.
Verrax, J., Stockis, J., Tison, A., Taper, H.S., and Buc Calderon, P.
(2006). Oxidative stress by ascorbate/menadione association
kills K562 human chronic myelogenous leukaemia cells and
inhibits its tumour growth in nude mice. Biochem. Pharmacol.
72, 671–680.
Verrax, J., Stockis, J., Vanbever, S., Taper, H., and Buc Calderon,
P. (2007). Role of glycolysis inhibition and Poly(ADP-ribose)
polymerase activation in necrotic-like cell death caused by
ascorbate/menadione-induced oxidative stress in K562 human
chronic myelogenous leukemic cells. Int. J. Cancer 120,
1192–1197.
Verrax, J., Pedrosa, R.C., Beck, R., Dejeans, N., Taper, H., and Buc
Calderon, P. (2009). In situ modulation of oxidative stress:
a novel and efficient strategy to kill cancer cells. Curr. Med.
Chem. 16, 1821–1830.
Verrax, J., Dejeans, N., Sid, B., Glorieux, C., and Buc Calderon, P.
(2011a). Intracellular ATP levels determine cell death fate of
cancer cells exposed to both standard and redox chemothera-
peutic agents. Biochem. Pharmacol. 82, 1540–1548.
Verrax, J., Beck, R., Dejeans, N., Glorieux, C., Sid, B., Pedrosa, R.C.,
Benites, J., Vasquez, D., Valderrama, J.A., and Buc Calderon, P.
(2011b). Redox-active quinones and ascorbate: an innovative
cancer therapy that exploits the vulnerability of cancer cells to
oxidative stress. Anticancer Agents Med. Chem. 11, 213–221.
Vetrano, A.M., Heck, D.E., Mariano, T.M., Mishin, V., Laskin, D.L.,
and Laskin, J.D. (2005). Characterization of the oxidase activity
in mammalian catalase. J. Biol. Chem. 280, 35372–35381.
Vlasits, J., Jakopitsch, C., Schwanninger, M., Holubar, P., and
Obinger, C. (2007). Hydrogen peroxide oxidation by catalase-
peroxidase follows a non-scrambling mechanism. FEBS Lett.
581, 320–324.
Wanders, R.J., Kos, M., Roest, B., Meijer, A.J., Schrakamp, G.,
Heymans, H.S., Tegelaers, W.H., van den Bosch, H., Schutgens,
R.B., and Tager, J.M. (1984). Activity of peroxisomal enzymes
and intracellular distribution of catalase in Zellweger syn-
drome. Biochem. Biophys. Res. Commun. 123, 1054–1061.
Wang, C.D., Sun, Y., Chen, N., Huang, L., Huang, J.W., Zhu, M., Wang,
T., and Ji, Y.L. (2016). The role of catalase C262T gene polymor-
phism in the susceptibility and survival of cancers. Sci. Rep. 6,
26973.
Warburg, O. (1923). Versuche an uberlebendem karzinomgewebe.
Biochem. Z. 142, 317–333.
Welsh, S.J., Williams, R.R., Birmingham, A., Newman, D.J., Kirkpat-
rick, D.L., and Powis, G. (2003). The thioredoxin redox inhibi-
tors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit
hypoxia-induced factor 1alpha and vascular endothelial growth
factor formation. Mol. Cancer Ther. 2, 235–243.
Wieacker, P., Mueller, C.R., Mayerova, A., Grzeschik, K.H., and
Ropers, H.H. (1980). Assignment of the gene coding for human
catalase to the short arm of chromosome 11. Ann. Genet. 23,
73–77.
Wink, D.A. and Mitchell, J.B. (1998). Chemical biology of nitric oxide:
insights into regulatory, cytotoxic, and cytoprotective mecha-
nisms of nitric oxide. Free Radic. Biol. Med. 25, 434–456.
Winternitz, M.C. and Meloy, C.R. (1908). On the occurrence of
catalase in human tissues and its variations in diseases. J. Exp.
Med. 10, 759–781.
Yano, S., Arroyo, N., and Yano, N. (2004a). Catalase binds Grb2 in
tumor cells when stimulated with serum or ligands for integrin
receptors. Free Radic. Biol. Med. 36, 1542–1554.
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM
1108      C. Glorieux and P. B. Calderon: Targeting catalase as new cancer treatment approach
Yano, S., Arroyo, N., and Yano, N. (2004b). SHP2 binds catalase and
acquires a hydrogen peroxide-resistant phosphatase activity
via integrin-signaling. FEBS Lett. 577, 327–332.
Zamocky, M. and Koller, F. (1999). Understanding the structure and
function of catalases: clues from molecular evolution and in
vitro mutagenesis. Prog. Biophys. Mol. Biol. 72, 19–66.
Zamocky, M., Furtmuller, P.G., and Obinger, C. (2008). Evolution of
catalases from bacteria to humans. Antioxid. Redox. Signal. 10,
1527–1548.
Zamocky, M., Furtmuller, P.G., and Obinger, C. (2010). Evolution of
structure and function of Class I peroxidases. Arch. Biochem.
Biophys. 500, 45–57.
Brought to you by | Bibliothèques de l'UCL
Authenticated
Download Date | 9/8/17 1:29 PM