Antiproliferative activity and apoptosis-inducing mechanism of L-securinine on human breast cancer MCF-7 cells

Abstract

Natural products have been discovered to be valuable sources of antitumor drugs. L-Securinine is a natural product extracted from the leaves or roots of Securinega suffruticosa Pall Rehd. The current study was done to investigate the molecular mechanisms of antitumor effects of L-securinine. The inhibitory activities of L-securinine on human breast cancer MCF-7 cells were studied in vitro by a Cell Counting Kit-8(cck8) assay. Flow cytometry was used to analyze the apoptotic ratio and cell cycle distribution of control and treated MCF-7 cells with L-Securinine. Real-time quantitative PCR was conducted to evaluate expression levels of apoptosis related genes P53, Bax, Bcl-2, Mtor, P70s6k. L-Securinine exhibited remarkable antiproliferation activities on MCF-7 cells in dose- and time-dependent manner (24, 48 and 72 h of incubation). A 48 h exposure to L-securinine at a concentration ranging from 0 to 40 microM resulted in a significant increase in apoptotic ratio. At both low and high concentrations, L-securinine preferably perturbed the cell cycle in MCF-7 cells by arrest of G1 phase. These results were further confirmed by the increased expression of bax, p53 and the decreased expression of bcl-2, mtor, p70s6k in a dose-dependent manner. In summary, these findings suggest that L-securinine has an anti-tumor effect against MCF-7 cells and could be further exploited as a potential lead in antitumor drug development.