Induction of apoptosis in colon cancer cells by nonsteroidal anti-inflammatory drugs
Yonsei Medical Journal
;
: 287-295, 1998.
Article
in English
| WPRIM
| ID: wpr-229304
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Protein Kinases
/
RNA, Messenger
/
Cell Survival
/
Anti-Inflammatory Agents, Non-Steroidal
/
Calcium
/
Tumor Suppressor Protein p53
/
Apoptosis
/
Cyclins
/
Colonic Neoplasms
/
HT29 Cells
Limits:
Humans
Language:
English
Journal:
Yonsei Medical Journal
Year:
1998
Type:
Article
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