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| Modulation of apoptosis and Bcl-2 expression by prostaglandin E-2 in human colon cancer cells |
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| Author(s): Sheng HM, Shao JY, Morrow JD, Beauchamp RD, DuBois RN |
| Source: CANCER RESEARCH Volume: 58 Issue: 2 Pages: 362-366 Published: JAN 15 1998 |
| Times Cited: 733 References: 33 |
| Abstract: 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 PGE(2) 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 PGE(2). Additionally, PGE(2) 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 PGE(2) 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: DuBois, RN (reprint author), Vanderbilt Univ, Med Ctr, Dept Med GI, MCN C-2104, Nashville, TN 37232 USA |
Addresses:
1. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA
2. Vanderbilt Univ, Med Ctr, Dept Cell Biol, Nashville, TN 37232 USA
3. Vanderbilt Univ, Med Ctr, Dept Surg, Nashville, TN 37232 USA
4. Vanderbilt Univ, Med Ctr, Ctr Mol Toxicol, Nashville, TN 37232 USA
5. Vet Affairs Med Ctr, Nashville, TN 37232 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PO BOX 11806, BIRMINGHAM, AL 35202 USA |
| Subject Category: Oncology |
| IDS Number: YR421 |
| ISSN: 0008-5472 |
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