Suicidal oxidative stress induced by certain antioxidants

Abstract

Well known antioxidants-coumarins (7,8-dihydroxy-4-methyl coumarin -DHMC and 7,8-diacetoxy-4-methyl coumarin DAMC) and flavanoids (quercetin-Q and quercetin penta-acetate-QPA) were investigatcd for their pro-oxidant effects in two human tumor cell lines. The breast carcinoma cell line (MDA-MB-468) was found to be more sensitive to treatment by

the drugs- DAMC, Q and QPA at 10<i>μ</i><i>M</i> than the glioma cell line (U-87MG), while DHMC was, non toxic in both cell lines at this concentration. In MDA-MB-468 distinct growth inhibition was observed by 48 hr post treatment. Paradoxically, An increase in the formazan production was revealed by MTT assay at this time indicating an increase in the production of free radicals. An increase in the levels of reactive oxygen species (ROS) was also confirmed by DCFH-DA assay. In cells treated with DAMC, Q and QPA an increase in the percentage of cells with the hypodiploid DNA content was, suggestive of

apoptotic cell death. Taken together, these results suggest that an increase in oxidativc stress caused by the pro-oxidant action of these drugs is responsible for cell death.