Delphinidin increases the sensitivity of ovarian cancer cell lines to 3‐bromopyruvate

Abstract

3‐Bromopyruvic acid (3‐BP) is a promising anticancer compound. Two ovary cancer (OC) cell lines, PEO1 and SKOV3, showed relatively high sensitivity to 3‐BP (half maximal inhibitory concentration (IC50) of 18.7 and 40.5 μM, respectively). However, the further sensitization of OC cells to 3‐BP would be desirable. Delphinidin (D) has been reported to be cytotoxic for cancer cell lines. We found that D was the most toxic for PEO1 and SKOV3 cells from among several flavonoids tested. The combined action of 3‐BP and D was mostly synergistic in PEO1 cells and mostly weakly antagonistic in SKOV3 cells. The viability of MRC‐5 fibroblasts was not affected by both compounds at concentrations of up to 100 μM. The combined action of 3‐BP and D decreased the level of ATP and of dihydroethidium (DHE)‐detectable reactive oxygen species (ROS), cellular mobility and cell staining with phalloidin and Mitotracker Red in both cell lines but increased the 2’,7’‐dichlorofluo-rescein (DCFDA)‐detectable ROS level and decreased the mitochondrial membrane potential and mitochondrial mass only in PEO1 cells. The glutathione level was increased by 3‐BP+D only in SKOV3 cells. These differences may contribute to the lower sensitivity of SKOV3 cells to 3‐BP+D. Our results point to the possibility of sensitization of at least some OC cells to 3‐BP by D.