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’-dichlorofluorescein (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.
Highlights
The term “ovarian cancer” (OC) includes several different types of cancer that all arise from cells of the ovary
Delphinidin did not affect the survival of MRC-5 fibroblasts in the concentration range studied (Table 1 and Figure 2b)
When cells were treated with D together with 3-Bromopyruvic acid (3-BP) employed at a concentration corresponding to the IC50 for a given cell line, D decreased further the survival of PEO1 cells, the decrease being weakly dependent of the D concentration in the concentration range of 25–100 μM
Summary
The term “ovarian cancer” (OC) includes several different types of cancer that all arise from cells of the ovary. Most commonly (in nearly 90%), tumors arise from the epithelium of the ovary [1]. The American Cancer Society estimates that, in 2020, about. 21,750 American women will be diagnosed with OC, and 13,940 women will die from the disease. The initial treatment for advanced-stage OC frequently includes a surgical staging or debulking procedure, followed by a combination of platinum and Taxol adjuvant chemotherapy [2,3]. Despite a high response rate to first-line chemotherapy, the majority of women with advanced stage OC will relapse, with the median progression free survival being 16 months after initial diagnosis. The five-year survival is dismal at less than
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