title: Akebia saponin PA induces autophagic and apoptotic cell death in AGS human gastric cancer cells.
abstract: In this study, we investigated the anticancer mechanism of akebia saponin PA (AS), a natural product isolated from Dipsacus asperoides in human gastric cancer cell lines. It was shown that AS-induced cell death is caused by autophagy and apoptosis in AGS cells. The apoptosis-inducing effect of AS was characterized by annexin V/propidium (PI) staining, increase of sub-G1 phase and caspase-3 activation, while the autophagy-inducing effect was indicated by the formation of cytoplasmic vacuoles and microtubule-associated protein 1 light chain-3 II (LC3-II) conversion. The autophagy inhibitor bafilomycin A1 (BaF1) 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-dependent apoptosis. Furthermore, AS activated p38/c-Jun N-terminal kinase (JNK), which could be inhibited by BaF1, and caspase-3 activation was attenuated by both SB202190 and SP600125, indicating that AS-induced autophagy promotes mitogen-activated protein kinases (MAPKs)-mediated apoptosis. Taken together, these results demonstrate that AS induces autophagic and apoptotic cell death and autophagy plays the main role in akebia saponin PA-induced cell death.
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Mei-Ying
authors.initials: MY
authors.lastname: Xu
authors.forename: Dong Hwa
authors.initials: DH
authors.lastname: Lee
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Joo
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Son
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D049917:Dipsacaceae / Q000737:chemistry; D020834:Ethnopharmacology; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D055670:Medicine, Korean Traditional; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D056910:Republic of Korea; D012503:Saponins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C587326:Akebia saponin PA; D000972:Antineoplastic Agents, Phytogenic; D015415:Biomarkers; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D012503:Saponins; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Akebia saponin PA; Apoptosis; Autophagy; MAPKs; mTOR