Ovarian cancer is a common and lethal cancer affecting women globally. Berbamine is a natural compound from the plant Berberis amurensis, which is used in Chinese traditional medicine. Recent studies have shown the anti-tumor effects of berbamine in several types of cancers but not in ovarian cancer. In the present study, we investigated the potential anti-tumor effects of berbamine in ovarian cancer and explored the underlying molecular mechanisms. Berbamine suppressed the cell viability of ovarian cancer cells in a concentration-dependent manner as revealed by methyl thiazolyl tetrazolium assay. Berbamine also suppressed the cell growth and invasion of ovarian cancer cells as measured by colony formation and cell invasion assays, respectively. Flow cytometry experiments showed that berbamine increased cell apoptotic rate and induced cell cycle arrest at G0/G1 phase in ovarian cancer cells. Western blot analysis showed that berbamine increased the protein levels of cleaved caspase-3, cleaved caspase-9, Bax, and decreased the protein level of Bcl-2 in ovarian cancer cells. Quantitative real-time PCR and western blot analysis demonstrated that berbamine treatment inhibited the Wnt/β-catenin signaling in ovarian cancer cells. The inhibitory effects of berbamine on cell viability and invasion of ovarian cancer cells can be partially reversed by lithium chloride (LiCl) treatment. Growth of tumors developed from SKOV3 cells was significantly suppressed in berbamine-treated group, and berbamine treatment enhanced caspase-3 and -9 cleavage and reduced β-catenin protein level in tumor tissues. In summary, berbamine exerts its anti-cancer effects in vitro and in vivo via induction of apoptosis, partially associated with the inhibition of Wnt/β-catenin signaling.

Berbamine has been shown to exhibit anti-cancer activities in various types of cancers. The effects of berbamine on colorectal colon cancer (CRC) have not been examined, and the present study aimed to investigate the anti-cancer effects of berbamine in CRC and explore its underlying molecular mechanisms. The effect of berbamine on the CRC cells was determined by MTT assay. Flow cytometry was performed to examine the effect of berbamine on cell apoptosis and cell cycle as well as mitochondrial membrane potential in CRC cell lines. The specific apoptosis-related factors were evaluated by western blot assay. In vivo anti-cancer effect of berbamine was assessed in SW480 xenografts. Berbamine suppressed the cell viability of CRC cells in concentration-dependent and time-dependent manners. Flow cytometry experiments showed that berbamine increased cell apoptotic rate and induced cell cycle arrest at G/G phase. Berbamine treatment also decreased the mitochondrial membrane potential in CRC cells. Western blot assay showed that berbamine increased the protein levels of p53, caspase-3, caspase-9, Bax and poly ADP ribose polymerase, and decreased the protein levels of Bcl-2 in CRC cells. Berbamine failed to increase the cell apoptotic rate in p53 mutant CRC cell lines. Tumor growth by grafted SW480 cells were significantly suppressed in berbamine group. Expression of p53, caspase-3 and -9 in tumor tissues was significantly up-regulated by berbamine. Berbamine exerts anti-cancer effects in vitro and in vivo via induction of apoptosis, partially associated with the activation of p53-dependent apoptosis signaling pathway.

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