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Role of caspase-3 in apoptosis of colon cancer cells induced by nonsteroidal anti-inflammatory drugs.

 Won Ho Kim  ;  Marie Yeo  ;  Myung Soo Kim  ;  Sang Bae Chun  ;  Eiu Cheol Shin  ;  Jeon Han Park  ;  In Suh Park 
 International Journal of Colorectal Disease, Vol.15(2) : 105-111, 2000 
Journal Title
 International Journal of Colorectal Disease 
Issue Date
Anti-Inflammatory Agents, Non-Steroidal/pharmacology* ; Apoptosis/drug effects* ; Apoptosis/physiology ; Caspase 3 ; Caspases/drug effects* ; Caspases/genetics ; Caspases/metabolism ; Cysteine Proteinase Inhibitors/pharmacology ; Enzyme Precursors/drug effects* ; Enzyme Precursors/genetics ; Enzyme Precursors/metabolism ; Gene Expression Regulation, Enzymologic/drug effects ; HT29 Cells/drug effects* ; HT29 Cells/enzymology ; HT29 Cells/pathology ; Humans ; Indomethacin/pharmacology* ; Oligopeptides/pharmacology ; Poly(ADP-ribose) Polymerases/metabolism ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription, Genetic/drug effects
Epidemiological studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of and mortality from colon cancer. In addition, NSAIDs reduce the number and the size of polyps in patients with familial adenomatous polyposis. The mechanisms responsible for the antineoplastic effect of NSAIDs are not yet completely understood, but one of the possible mechanisms is an induction of apoptosis. We explored the role of caspase-3, a major apoptosis-executing enzyme, in NSAID-induced apoptosis of colon cancer cell line HT-29. Treatment of HT-29 cells with indomethacin induced a dramatic increase in caspase-3-like protease activity measured by a cleavage of the fluorogenic substrate Ac-DEVD-AMC. Western blot analysis showed that indomethacin treatment led both to decrease in procaspase-3 and to cleavage of its substrate poly(ADP-ribose) polymerase (PARP). Furthermore, the caspase-3-like protease inhibitor Ac-DEVD-CHO attenuated indomethacin-induced DNA fragmentation dose dependently. However, mRNA expression of CASP genes was not affected by the addition of indomethacin, highlighting the importance of posttranslational modification of this enzyme for the activation. These results suggest that NSAIDs, including indomethacin, induce apoptosis in colon cancer cells through a caspase-3 dependent mechanism which may contribute to the chemopreventive functions of these agents.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
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