Berberine Exhibits Antitumor Effects in Human Ovarian Cancer Cells

Background: Berberine is an extract of a traditional Chinese herbal medicine and has been shown to inhibit the proliferation and induce apoptosis in a wide variety of tumour cells. However, the effects of Berberine in ovarian cancer cells are unknown. Aims: To investigate the potential anti-cancer effects of Berberine in human ovarian cancer cells. Methods: Cell proliferation was evaluated by a MTT assay. Apoptosis was determined by using Annexin V/PI staining and transmission electron microscopy. The methylation status of the hMLH1 promoter CpG islands was analysed by using methylation-specific polymerase chain reaction (MSP). mRNA expression of BCLM-2, BAX, survivin and HMLH1 was quantified by real-time fluorescence quantitative RT-PCR. Results: Berberine significantly inhibited the proliferation of SKOV3 cells in a dose- and time-dependent manner. It also dosedependently induced apoptosis, possibly through down-regulating the anti-apoptotic genes BCL-2; and survivin, and up-regulating the pro-apoptotic gene BAX. When combined with cisplatin, Berberine showed a strong synergistic anticancer effect against ovarian cancer cells. In addition, Berberine was found to restore the demethylation status of the hMLH1 promoter and up-regulate the mRNA expression of hMLH1. Conclusion: Berberine possesses antitumor effect via inhibition of cell proliferation and induction of apoptosis in ovarian cancer cells. Berberine could synergistically enhance the cell killing effect of other antitumor agents such as cisplatin. Further studies are essential to explore the therapeutic potential of Berberine either alone or in combination with other anticancer agents in patients with ovarian cancer.