Piperine alkaloid induces anticancer and apoptotic effects in cisplatin resistant ovarian carcinoma by inducing G2/M phase cell cycle arrest, caspase activation and inhibition of cell migration and PI3K/Akt/GSK3β signalling pathway.

Purpose Ovarian cancer is one the prevalent cancers in women and is responsible for 5% of all the cancer-related mortality. Owing to late diagnosis, frequent relapses, side effects of chemotherapy, development of drug resistance, there is pressing need to screen out novel and effective treatment options. Herein, we examined the anticancer effects of a secoiridoid glycoside Piperine against ovarian cancer cells. Methods CCK8 assay was used to examine the anti-proliferative effects. DAPI and annexin V/propidium iodide (PI) staining assays were used to examine apoptotic cell death. Cell cycle analysis was performed by flow cytometry. The protein expressions were examined by western blotting. Results Piperine inhibited the growth of the ovarian cancer OVACAR-3 cell with IC50 of 28 µM. In contrast, Piperine had low cytotoxic effects on the normal astrocytes (SV40) cells with an IC50 of 200 µM. Also, Piperine exerted antiproliferative effects on the OVACAR-3 ovarian cancer cells by apoptotic cell death. This was concomitant with upregulation of apoptotic proteins such as caspase 3 and 9 and Bax expressions. Piperine also induced arrest of the OVACAR-3 cells at the G2/M phase of the cell cycle. Finally, Piperine also blocked the PI3K/Akt/GSK3β signal transduction pathway in OVACAR-3 ovarian cancer cells. Conclusions These results suggest that Piperine exerts potent anticancer effects on ovarian cancer cells and may prove beneficial in the management of ovarian cancer.