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together, our results suggest that the suppression of IDPm activity resulted in the disruption of cellular redox balance and subsequently exacerbates EGCG-induced apoptotic cell death in HeLa cells. These results might have implications for developing an effective combination modality in cancer treatment.
doi:10.1016/j.freeradbiomed.2011.10.333
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Oxidative Stress Induction and Antitumor Effect of Two Fenilaminonaftoquinones Against the Ehrlich Ascites Carcinoma
Karina Bettega Felipe1, Mirelle S Farias1, Tania M F Gunther1, Nadia F Bucker1, Maicon Roberto Kviecinski1, Fabiana Ourique1, Valdelucia V.M.A.S Grinevicius1, Geremias Reginaldo1, Benites J2, Pedro Buc Calderon3, and Rozangela Curi Pedrosa1 1 2 universidade Federal De Santa Catarina, Departamento de Ciencias Qumicas y Farmacuticas, Universidad Arturo Prat, 3 Iquique, Toxicology and Cancer Biology Research Group, Louvain Drug Research, Institute Universit Catholique Objective: Synthetic quinones have been researched for cancer chemotherapy, since some of them have potential antitumor activities, as well doxorubicin belong to the same drug class and a chemotherapeutic agent, whose action is also due to its ability to generate free radicals. the aim of this work was to verify if the antitumor effect of two synthetic quinones (Q7 and Q7A) could be related to oxidative stress induction. Methods: EhrIich ascites carcinoma (EAC) was inoculated in isogenic Balb/c male mice (~20g b.w., n=6) and this moment was taken as day 0. Intraperitoneal treatments with Q7 and Q7A (1mg/Kg per day) started on the first day and on tenth the animals were sacrificed. Negative Control (NC) received only saline. Their ascitic fluid was collected and used for the analysis. the following parameters were assessed: inhibition of tumor growth, percent of necrotic and apoptotic cells, as well as lipid peroxidation, activities of superoxide dismutase and catalase. Results were expressed by means and standard deviation and were analyzed using one-way ANOVA and Tukey-Kramers test. a P-value < 0.05 was considered to be statistically significant. Results: Q7 and Q7A decreased the tumor growth(Q7= 64.3; Q7A= 57.2; NC=0%), and increased the percent of necrotic cells(Q7= 19.5; Q7A= 45.5; NC=2.4%) when compared to NC. Only Q7 was able to increase the levels of lipid peroxidation(Q7= 14.3 3.6; Q7A= 8.5 1.4; NC= 6.2 4,0 mol/mg protein). Furthermore, the quinone treatments increased the superoxide dismutase(Q7= 71.3 4.6; Q7A= 27.8 2.0; NC= 13.2 5.0 USOD/mg protein) and catalase activities (Q7= 9.33.4; Q7A= 27.91.2; NC= 2.92.3 min/ mg protein). Conclusion: These findings suggest that the antitumor activity of Q7 and Q7A could be related to induction of free radical generation. Keywords: Fenilaminonaftoquinones; antitumor effect; ehrlich ascites carcinoma
doi:10.1016/j.freeradbiomed.2011.10.332
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Attenuated mitochondrial NADP+-dependent isocitrate dehydrogenase activity enhances EGCGinduced apoptosis
Kyu Ho Jung1, Kil in Sup1, and Jeen-Woo Park1 1 Kyungpook National University (-)-Epigallocatechin-3-gallate (EGCG), a well-known chemopreventive factor, induces cancer cells undergoing apoptosis. Over the last several years, we have shown that the + mitochondrial NADP -dependent isocitrate dehydrogenase (IDPm) functions as an antioxidant and anti-apoptotic protein by supplying NADPH to antioxidant systems. Here, we show that EGCG induced the inactivation of IDPm as a purified enzyme and in cultured cancer cells in a dose- and time-dependent manner. Loss of enzyme activity was associated with the depletion of the thiol groups in protein. in addition, transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly attenuated the activity of IDPm and substantially enhanced EGCG-induced apoptosis as indicated by the morphological evidence of apoptosis, DNA fragmentation, and the modulation of mitochondrial function and apoptotic marker proteins. Taken
doi:10.1016/j.freeradbiomed.2011.10.334
SFRBM 2011
S127