title: A triterpenoid saponin from Adenophora triphylla var. japonica suppresses the growth of human gastric cancer cells via regulation of apoptosis and autophagy.
abstract: In the present study, we investigated the effects of 3-O-β-D-galactopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucuronopyranosyl-28-O-[α-L-arabinopyranosyl-(1 → 4)-α-L-arabinopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 2)-β-D-fucopyranosyl] quillaic acid, named compound 1, on the induction of apoptosis and autophagy in human gastric cancer AGS cells. Compound 1, a triterpenoid saponin isolated from the root of Adenophora triphylla var. japonica, effectively inhibited the growth of AGS cells by inducing apoptosis, as well as autophagy. Apoptosis by compound 1 treatment was associated with activation of caspases, release of cytochrome c, and increased ratio of Bax/Bcl-2. Autophagy by compound 1 treatment was indicated by LC3-II protein expression. We also found an increase in phosphorylation of p38 and JNK and a decrease in phosphorylation of ERK and Akt after compound 1 treatment. Furthermore, pretreatment with p38 inhibitor SB202190 completely inhibited compound 1-induced activation of caspases and cleavage of PARP1, whereas pretreatment with SB202190 synergistically increased the protein expression of LC3-II. These results suggest that compound 1 distinctly induces apoptotic and autophagic cell death and the increased autophagy by SB202190 protects compound 1-induced AGS cell death. Our findings provide an important clue for exploring the potential anticancer role of compound 1.
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea.
authors.forename: Jaemoo
authors.initials: J
authors.lastname: Chun
authors.forename: Minseok
authors.initials: M
authors.lastname: Kang
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D029422:Campanulaceae / Q000737:chemistry*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases