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

 Sung Pyo Hong  ;  Sung Ho Ha  ;  In Suh Park  ;  Won Ho Kim 
 YONSEI MEDICAL JOURNAL, Vol.39(4) : 287-295, 1998 
Journal Title
Issue Date
Anti-Inflammatory Agents, Non-Steroidal/pharmacology* ; Apoptosis/drug effects* ; Calcium/metabolism ; Cell Survival/drug effects ; Colonic Neoplasms/pathology ; Colonic Neoplasms/prevention & control* ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/biosynthesis ; Cyclins/genetics ; HT29 Cells ; Humans ; Protein Kinases/physiology ; Proto-Oncogene Proteins c-bcl-2/analysis ; RNA, Messenger/analysis ; Tumor Suppressor Protein p53/physiology
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
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