Yonsei Med J.  1998 Aug;39(4):287-295. 10.3349/ymj.1998.39.4.287.

Induction of apoptosis in colon cancer cells by nonsteroidal anti-inflammatory drugs

• Hong SP
• Ha SH
• Park IS
• Kim WH

• KMID: 711560
• DOI: http://doi.org/10.3349/ymj.1998.39.4.287

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.

Keyword

NSAIDs; colon cancer; apoptosis; cell cycle; P21(WAF-1)

MeSH Terms

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