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

Phytomedicine. 2018 Dec 1;51:139-150. doi: 10.1016/j.phymed.2018.10.012. Epub 2018 Oct 10.

Abstract

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.

Keywords: Afrocyclamin A; Apoptosis; Autophagy; PI3K/Akt/mTOR; Triterpene saponin.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Autophagy / drug effects*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphoinositide-3 Kinase Inhibitors
  • Phytochemicals / pharmacology
  • Primulaceae / chemistry*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Saponins / pharmacology*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism
  • Triterpenes / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Phosphoinositide-3 Kinase Inhibitors
  • Phytochemicals
  • Saponins
  • Triterpenes
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt