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Prolonged activation of mitogen-activated protein kinases during NSAID-induced apoptosis in HT-29 colon cancer cells

Authors
 Tae Kim  ;  Soo Jin  ;  Won Kim  ;  Eun Kang  ;  Kang Choi  ;  Hyun Kim  ;  Sung Shin  ;  Jin Kang 
Citation
 INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, Vol.16(3) : 167-173, 2001 
Journal Title
 INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 
ISSN
 0179-1958 
Issue Date
2001
Keywords
Nonsteroidal anti-inflammatory drugs (NSAIDs) ; Colon cancer ; Apoptosis ; Mitogen-activated protein (MAP) kinases ; p38 MAP kinase
Abstract
The mechanisms of the antineoplastic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) still are unknown, but the induction of apoptosis is one of the possible mechanisms. We attempted to demonstrate the role of mitogen-activated protein (MAP) kinases, generally considered to be important mediators of proliferative and apoptotic signals, in NSAID-induced colon cancer cell apoptosis. Apoptosis was detected by demonstration of DNA fragmentation in agarose gel electrophoresis. Cell death was assessed by trypan blue dye exclusion method. MAP kinase activation was assessed by Western blot using phosphospecific antibodies to MAP kinases. Kinase assay using activating transcription factor-2 (ATF-2) fusion protein as a substrate was also performed for measuring p38 MAP kinase activity. For the inhibition of p38 MAP kinase, pyridinylimidazole compound (SB203580) was utilized. Caspase-3 activity was measured using the tetrapeptide fluorogenic substrate Ac-DEVD-AMC. Treatment of HT-29 cells with NSAIDs results in time- and dose-dependent induction of apoptosis, accompanied by sustained activation of all three MAP kinase subfamilies. The SB203580, a p38 MAP kinase inhibitor, reduced indomethacin-induced cell death by 43%, while PD098059, a MAPK/ERK kinase (MEK)1 inhibitor, did not affect cell death. p38 MAP kinase and caspase-3 activation were not significantly interlinked in indomethacin-induced apoptosis. From these results, we conclude that NSAIDs can induce prolonged activation of MAP kinases in colon cancer cells and that, of these, p38 MAP kinase may play a partial but significant role in indomethacin-induced apoptosis.
Full Text
http://link.springer.com/article/10.1007/s003840100301
DOI
10.1007/s003840100301
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Jin Kyung(강진경)
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Shin, Sung Kwan(신성관) ORCID logo https://orcid.org/0000-0001-5466-1400
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141896
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