12th World Cancer Conference
Carol Davila University of Medicine and Pharmacy, Romania
Title: Cytotoxic effect of doxorubicin/menadione combination on human leukemia Jurkat cells
Biography: Maria-Teodora Ilie
The combined cytotoxic effect of the anticancer drug doxorubicin (DOX) and menadione (MD) was assessed in human leukemia Jurkat cells. Oxidative status, apoptosis/necrosis and cell cycle were determined using flow cytometry. Within 4 h of exposure, MD induced oxidative stress and reduced the fraction of viable cells, in a cooperative manner (IC50=11.5 µM, Hill coefficient H=2.40). Addition of 0.5 µM DOX inhibited the oxidant effect of MD presumably by altering the affinity of MD for respiratory complex I (IC50=22.0 µM, H=2.46). In 18-hour treatment, DOX dose-dependently generated significant oxidative stress (IC50=0.6 µM, H=2). In combination with 7.5 µM and 15 µM MD, the oxidative stress generation was increased and DOX cooperativity was enhanced and not modified, respectively. MD induced cell death in a dose-dependent manner (H=2.73) and association with 100 nM DOX enhanced cell death and MD cooperativity (H=5.40). Within 18 h of exposure, DOX induced apoptosis, which was enhanced by 15 µM MD. MD dose-dependently altered the cell cycle arrest in G2/M promoted by 100 nM DOX. After a 4 h treatment, both MD and DOX induced mitochondrial depolarization (IC50=6.75 µM, H=1.18 and IC50=0.200 nM, H=0.30, respectively). In conclusion, MD could increase the chemotherapeutic potential of doxorubicin.