Afrocyclamin A, a triterpene saponin, induces apoptosis and autophagic cell death via the PI3K/Akt/mTOR pathway in human prostate cancer cells.

BACKGROUND: Afrocyclamin A, an oleanane-type triterpene saponin, was isolated from Androsace umbellata which used as a traditional herbal medicine.
PURPOSE: This study aimed to explore the anticancer activity of afrocyclamin A on human prostate cancer cells in vitro as well as in vivo.
METHODS: Cytotoxicity, cell cycle distribution, apoptosis, and autophagic cell death were measured following exposure to afrocyclamin A. In vivo antitumor activity of afrocyclamin A was assessed in a xenograft model. The protein levels of p-Akt, p-mTOR, Bax, Bcl-2, caspase-3, and caspase-9 were quantified using western blot analysis.
RESULTS: In DU145 cells, afrocyclamin A increased cytotoxicity, caused changes in cell morphology, and induced sub-G0/G1 phase indicating increased apoptosis. Afrocyclamin A robustly induced autophagic cell death as demonstrated by the conversion of LC3B-I to LC3B-II, and the formation of autophagic vacuoles as revealed by western blot analysis and fluorescence staining, respectively. Afrocyclamin A also inhibited the phosphorylation of PI3K, Akt, and mTOR, suggesting their role in afrocyclamin A induced cell death. In addition, afrocyclamin A inhibited cell migration and invasion in concentration and time-dependent manners. In an in vivo xenograft model, afrocyclamin A inhibited the growth of DU145 cells.
CONCLUSION: Afrocyclamin A has anticancer activity via the PI3K/Akt/mTOR pathway, which leads to cell death.