Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells

Previously, we have shown that forced expression of prostaglandin endoperoxide synthase-2 [also called cyclooxygenase (COX) 2] leads to inhibition of programmed cell death in intestinal epithelial cells. More recently, we have demonstrated that growth of human colonic cancer xenografts is inhibited...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1998-01, Vol.58 (2), p.362-366
Main Authors: SHENG, H, SHAO, J, MORROW, J. D, BEAUCHAMP, R. D, DUBOIS, R. N
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Biological and medical sciences
Clone Cells - drug effects
Colonic Neoplasms - drug therapy
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors - pharmacology
Dinoprostone - metabolism
Dinoprostone - pharmacology
Dose-Response Relationship, Drug
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Immunoblotting
Isoenzymes - metabolism
Medical sciences
Membrane Proteins
Mice
Mice, Nude
Neoplasms, Experimental - pathology
Prostaglandin-Endoperoxide Synthases - metabolism
Proto-Oncogene Proteins c-bcl-2 - metabolism
Pyrazoles - pharmacology
Stem Cells - drug effects
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Transplantation, Heterologous
Tumor Cells, Cultured - drug effects
Tumors
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Summary:Previously, we have shown that forced expression of prostaglandin endoperoxide synthase-2 [also called cyclooxygenase (COX) 2] leads to inhibition of programmed cell death in intestinal epithelial cells. More recently, we have demonstrated that growth of human colonic cancer xenografts is inhibited by treatment with a highly selective COX-2 inhibitor in tumors that express COX-2 (HCA-7) but not in those that lack COX-2 expression (HCT-116). To explore the biochemical mechanisms involved in these effects, we have evaluated the role of COX-2-derived eicosanoid products on programmed cell death in human colon cancer cells. Here we report that PGE2 treatment of human colon cancer cells leads to increased clonogenicity of HCA-7, but not HCT-116 cells. Treatment with a highly selective COX-2 inhibitor (SC-58125) decreases colony formation in monolayer culture and this growth inhibition was reversed by treatment with PGE2. Additionally, PGE2 inhibits programmed cell death caused by SC-58125 and induces Bcl-2 expression, but did not affect Bcl-x or Bax expression in human colon cancer (HCA-7) cells. Therefore, decreased cell death caused by PGE2 would enhance the tumorigenic potential of intestinal epithelial cells. Thus, these results may help to explain a component of the mechanism by which COX inhibitors prevent colorectal cancer in humans.
ISSN:0008-5472
1538-7445