Planta Med 2012; 78 - PD74
DOI: 10.1055/s-0032-1320432

Akebia saponin PA induces autophagic and apoptotic cell death via MTOR and MAPK pathways in gastric cancer cells

MY Xu 1, EJ Joo 1, DH Lee 2, KH Son 2, YS Kim 1
  • 1Collage of Pharmacy/Natural Products Research Institute, Seoul National University, Seoul 151–742, Korea
  • 2Department of Food and Nutrition, Andong National University, Andong 760–749, Korea

Akebia saponin PA (AS), a natural product isolated from Dipsacus asperoides, exhibits cytotoxicity in several cancer cell lines through a mechanism that is not yet defined. To better understand AS-induced cell death and its underlying mechanism, experiments were performed in human gastric cancer cells. The present studies illustrate that AS-induced cell death is caused by autophagy and apoptosis. The autophagy-inducing effect of AS was observed at an early stage, as indicated by the formation of cytoplasmic vacuoles and microtubule-associated protein 1 light chain-3 II (LC3-II) conversion while apoptosis-induction was characterized by DNA fragmentation, flow cytometric analysis, caspase-3 activation and the cleavage of poly(ADP-ribose)polymerase-1 (PARP-1). The autophagy inhibitor bafilomycin A1 decreased AS-induced cell death and caspase-3 activation, but caspase-3 inhibitor Ac-DEVD-CHO did not affect LC3-II accumulation or AS-induced cell viability, suggesting that AS induces autophagic cell death and autophagy contributes to caspase-3 mediated apoptosis. Molecular mechanism studies indicate that AS-induced autophagy is regulated by the p53/AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) and Akt/mTOR signaling pathways and enhanced autophagic flux promotes mitogen-activated protein kinases (MAPKs) modulated apoptosis.