12th World Cancer Conference
Carol Davila“ University of Medicine and Pharmacy, Romania
Title: Cytotoxic effects of doxorubicin on human leukemia Jurkat cells. Drug interactions with quercetin
Biography: Vlad Cosoreanu
The cytotoxic effect of the anticancer drug doxorubicin (DOX) in a human leukemia Jurkat T cell line was determined by flow cytometric assays of cell cycle, apoptosis/necrosis, oxidative status and mitochondrial Ca2+ level. 18-h and 45-h DOX-exposure induced apoptosis with IC50 = 951 nM, and IC501 = 135 nM/IC502 = 1.92 mM (bimodal), respectively, which was accompanied by significant oxidative stress generation (IC50 = 620 nM). The addition of the flavonoid quercetin (QC) (10 mM) resulted in a significat decrease of cell viability for DOX levels <100 nM. DOX induced cell cycle arrest displaying a trimodal distribution, so that low, intermediate and high doses of DOX specifically produced G2/M, S and G0/G1 blockage with IC50 of 49 nM, 464 nM and 1866 nM, respectively. QC (15 mM) exerted strong antioxidant effects, reducing DOX-induced oxidative stress and apoptosis (IC50 = 2119 nM and 4897 nM, repectively). However, cell cycle arrest induced by low and moderate doses of DOX was maintained in the presence of QC levels <25 mM. DOX induced substantial mitochondrial depolarization within 4-h in a dose-dependent manner (IC50 = 0.200 nM). A 15-min exposure to DOX induced an immediate decrease of mitochondrial Ca2+ level IC50 = 18.3 mM and the addition of QC (15 mM) amplified this effect for a concentration of DOX <20 mM, but resulted in an increase of mitochondrial Ca2+ for higher concentrations. This work was supported by a fellowship of the Romanian Ministry of Education, UEFISCDI, for Young Researchers, project number 6/2015.