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latycodin D induces anoikis and caspase-mediated apoptosis via p38 MAPK in AGS human gastric cancer cells

Cited 57 time in Web of Science Cited 63 time in Scopus
Authors
Chun, Jaemoo; Joo, Eun Ji; Kang, Minseok; Kim, Yeong Shik
Issue Date
2013-02
Publisher
Wiley Periodicals, Inc
Citation
Journal of Cellular Biochemistry Vol.114 No.2, pp. 456-470
Keywords
복합학PLATYCODIN DAPOPTOSISp38 MAPKAGSANOIKISAP-1
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.
ISSN
0730-2312 (print)
1097-4644 (online)
Language
English
URI
https://hdl.handle.net/10371/91113
DOI
https://doi.org/10.1002/jcb.24386
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College of Pharmacy (약학대학)Dept. of Manufacturing Pharmacy (제약학과)Journal Papers (저널논문_제약학과)
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