Suppression of taxanes cytotoxicity by citrus flavonoid hesperetin in PPC-1 human prostate cancer cells

Abstract

Background/Aim: More than half of prostate cancer patients use, in addition to conventional therapies, some kind of complementary medicine, including flavonoidrich products. However, knowledge about the co-effects of flavonoids with cytotoxic chemotherapies is still rather poor. Therefore, this study was undertaken to assess the cytotoxic activity of flavonoids and their interactions with taxanes in human advanced prostate cancer cells. Materials and Methods: Cytotoxicity of different flavonoids and their effects on the efficacy of docetaxel and cabazitaxel were studied in the human metastatic prostate cancer cell line PPC-1, using MTT colorimetric assay. Results: Both taxanes suppressed the viability of PPC-1 cells with IC50 values in the nanomolar range. Tested flavonoids exerted cytotoxic activity only at high micromolar concentrations or revealed no remarkable effect on cell survival. Simultaneous treatment of cells with taxanes and flavonoids baicalein, chrysin, luteolin, fisetin, quercetin, genistein or daidzein did not lead to any change in chemotherapy-induced cytotoxicity. However, simultaneous exposure of cells to hesperetin and taxanes resulted in 9.8- and 13.1-fold reduction in cytotoxicity of docetaxel and cabazitaxel, respectively. Conclusion: Flavonoid hesperetin remarkably suppressed the cytotoxic efficacy of taxanes in prostate cancer cells. Therefore, caution is required from prostate cancer patients who take hesperetin-containing oral supplements.