Antiproliferative activity and apoptosis-inducing mechanism of L-securinine on human breast cancer MCF-7 cells.
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.
Maidong
M
Li
Shuwen
S
Han
Gang
G
Zhang
Ying
Y
Wang
Zhaoning
Z
Ji
D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001381:Azepines / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006572:Heterocyclic Compounds, Bridged-Ring / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D001381:Azepines; D006572:Heterocyclic Compounds, Bridged-Ring; D007783:Lactones; D010880:Piperidines; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C000785:securinine