tailieunhanh - Báo cáo khoa học: The role of antioxidants in the cytotoxicity of chemotherapeutic drugs

A number of drugs used in cancer chemotherapy induce oxidative stress by generation of oxygen free radicals (ROS) which might be an alternative mechanism for their cytotoxic effect via indu-cing apoptosis. In order to clarify the roles of antioxidants in chemotherapy, we investigated Quercetin (3,3’,4’,5,7-pentahyd-roxyflavone) and N-acetylcysteine (NAC) in different cell types treated with anticancer drugs. We studied cytotoxic activity of Topotecan alone and/or in combination with Quercetin in two human breast cancer cell lines, MCF-7 and MDA-MB-231. . | Abstracts 3. Molecular Basis of Disease Oxidative Stress The role of antioxidants in the cytotoxicity of chemotherapeutic drugs T. Ozben H. Akbas I. Akan S. Akan and M. Timur Department of Biochemistry Faculty of Medicine Akdeniz University Antalya Turkey. E-mail ozben@ A number of drugs used in cancer chemotherapy induce oxidative stress by generation of oxygen free radicals ROS which might be an alternative mechanism for their cytotoxic effect via inducing apoptosis. In order to clarify the roles of antioxidants in chemotherapy we investigated Quercetin 3 3 4 5 7-pentahyd-roxyflavone and N-acetylcysteine NAC in different cell types treated with anticancer drugs. We studied cytotoxic activity of Topotecan alone and or in combination with Quercetin in two human breast cancer cell lines MCF-7 and MDA-MB-231. We also investigated the effect of NAC on MRP1-mediated doxorubicin and vincristine cytotoxicity in Human Embryonic Kidney HEK293 and its MrPi transfected 293MRP cells. The viability of the cells was measured using the colorimetric MTT 3- 4 5 -dimethylthiazol-2-yl -2 5-diphenyltetrazolium bromide assay. Intracellular ROS was measured using fluorometric 2 7 -dichlorodihydrofluorescein diacetate DCFH-DA assay. Our data indicated increased oxidative status in MCF-7 and MDA-MB-231 cells exposed to Topotecan. Treatment with Quercetin did not inhibit ROS generation and enhanced cytotoxicity of Topotecan in both cells. In contrast NAC enhanced resistance against doxorubicine and vincristine in MRP1 overexpressing cells. We conclude that Quercetin and NAC may have diverse effects in the cytotoxicity of chemotheurapeutic drugs depending on their other pharmacological properties which may predominate their antioxidant effects. Oxidized protein degradation and repair in ageing and oxidative stress B. Friguet Laboratoire de Biologie et Biochimie Cellulaire du Vieillissement Universite Denis Diderot - Paris 7 Paris France. E-mail .