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

Hongmiao Sheng, Jinyi Shao, Jason D. Morrow, R. Daniel Beauchamp, Raymond N. DuBois

Research output: Contribution to journalArticle

1077 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)362-366
Number of pages5
JournalCancer Research
Volume58
Issue number2
StatePublished - Jan 15 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sheng, H., Shao, J., Morrow, J. D., Beauchamp, R. D., & DuBois, R. N. (1998). Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Research, 58(2), 362-366.