title: Platycodin D induces anoikis and caspase-mediated apoptosis via p38 MAPK in AGS human gastric cancer cells.
abstract: Mitogen-activated protein kinases (MAPKs) cascades play important roles in cell proliferation, death, and differentiation in response to external stimuli. However, the precise role of MAPKs in platycodin D (PD)-induced cytotoxicity remains unclear. In this study, we investigated the anticancer effect of PD and its underlying mechanism on AGS human gastric cancer cells. PD significantly inhibited cell proliferation and induced anoikis, which is a form of apoptosis in which cells detach from the substrate. It showed phosphatidylserine externalization, DNA fragmentation, increase of sub-G1 phase, and activation of caspases in a dose- and time-dependent manner. This apoptosis has been associated with the extrinsic pathway via Fas-L and the intrinsic pathway via mitochondrial Bcl-2 family members. Moreover, PD led to the phosphorylation of stresses-activated protein kinases such as JNK and p38, followed by the activation of AP-1. However, pretreatment with SB203580 (a p38 specific inhibitor) suppressed PD-induced p38 and AP-1 activation, and subsequently attenuated the PD-induced apoptosis in AGS cells. These results suggest that p38 activation is responsible for PD-induced apoptosis in AGS cells and PD might be useful for the development as the anticancer agent of gastric cancer.
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: Eun Ji
authors.initials: EJ
authors.lastname: Joo
authors.forename: Minseok
authors.initials: M
authors.lastname: Kang
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D023102:Anoikis / Q000187:drug effects; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012503:Saponins / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D011725:Pyridines; D012503:Saponins; D018808:Transcription Factor AP-1; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; C108953:platycodin D; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; C093642:SB 203580