Induction of apoptosis in colon cancer cells by nonsteroidal anti-inflammatory drugs.
10.3349/ymj.1998.39.4.287
- Author:
Sung Pyo HONG
1
;
Sung Ho HA
;
In Suh PARK
;
Won Ho KIM
Author Information
1. Department of Internal Medicine, Pundang Cha Hospital, Pochon Cha Medical University, Sungnam, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
NSAIDs;
colon cancer;
apoptosis;
cell cycle;
P21(WAF-1)
- MeSH:
Anti-Inflammatory Agents, Non-Steroidal/pharmacology*;
Apoptosis/drug effects*;
Calcium/metabolism;
Cell Survival/drug effects;
Colonic Neoplasms/prevention & control*;
Colonic Neoplasms/pathology;
Cyclins/genetics;
Cyclins/biosynthesis;
HT29 Cells;
Human;
Protein Kinases/physiology;
Protein p53/physiology;
Proto-Oncogene Proteins c-bcl-2/analysis;
RNA, Messenger/analysis
- From:Yonsei Medical Journal
1998;39(4):287-295
- CountryRepublic of Korea
- Language:English
-
Abstract:
Epidemiological studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of colon cancer. In addition, NSAIDs reduce the number and size of polyps in patients with familial adenomatous polyposis. The mechanisms of the anti-neoplastic effect of NSAIDs are still far from complete understanding, but one possible mechanism is the induction of apoptosis. Several lines of evidence suggest that NSAIDs-induced apoptosis in colon cancer cells are mediated through the cyclooxygenase (COX)-independent pathway. In this study we explored the mechanism of NSAIDs-induced apoptosis in the colon cancer cell line, HT-29. We confirmed that NSAIDs induce apoptosis in HT-29 cells irrespective of their COX-selectivity. Indomethacin enhanced the expression of p21waf-1 in HT-29 cells. However the expression of apoptosis-related genes such as Fas, bcl-2 and bax was not affected by indomethacin. Intra- and extra-cellular calcium chelators, protein tyrosine kinase (PTK) inhibitor, protein kinase A (PKA) inhibitor and protein kinase C (PKC) inhibitors did not influence indomethacin-induced apoptosis in HT-29 cells. We concluded that NSAIDs-induced apoptosis in colon cancer cells may be independent from signals transducted through [Ca++]i, PTK, PKA, PKC or the expression of apoptosis-related genes. In contrast, our results demonstrating the induction of p21waf-1 transcription by NSAIDs suggest the possible association of NSAIDs-induced apoptosis and cell-cycle control in colon cancer cells.
