Bioassay-guided isolation of phenolic apoptosis inducer anticancer agents from Berberis vulgaris fruits

Background: Cancer development is a multi-stage process in which apoptosis plays an important role. Apoptotic agents from natural products like phenolic compounds can be used effectively in the treatment of cancer. Berberis vulgaris L. fruits are a rich source of natural phenolic compounds and have been evaluated for their apoptotic effects. Objective: this study was carried out to evaluate the apoptotic effect of B. vulgaris fruits in normal and cancerous cells by investigating p53, Bax, and Bcl-2 genes expression and identifying an active compound. Methods: B. vulgaris fruits were extracted with ethanol using maceration method. To yield an active compound, the extract was divided into fractions and subfractions that could be evaluated using chromatography techniques, and the purified compound structure was determined by nuclear magnetic resonance (NMR). The cytotoxic activity of the selected fraction against 3T3 and MCF-7 cell lines along with its effect on the mRNA apoptosis regulating genes like p53, Bax, and Bcl-2 were investigated subsequently. Results: Results showed that B. vulgaris extract increased the mRNA level of p53 and Bax and decreased Bcl-2 mRNA level in cancer cell lines. The structure of the purified compound was determined as the 3-caffeoylquinic acid (chlorogenic acid). Conclusion: B. vulgaris fruit has in vitro antineoplastic activity by stimulating cellular apoptosis via increasing the levels of p53 and Bax proteins and decreasing Bcl-2 and comprises chlorogenic acid as one of its phenolic phytochemicals.