Sulindac sulfone inhibits K-ras-dependent cyclooxygenase-2 expression in human colon cancer cells

M. T. Taylor, K. R. Lawson, N. A. Ignatenko, S. E. Marek, D. E. Stringer, B. A. Skovan, E. W. Gerner

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Both the sulfide and sulfone metabolites of sulindac, a nonsteroidal anti-inflammatory drug, display anticarcinogenic effects in experimental models. Sulindac sulfide inhibits cyclooxygenase (COX) enzyme activities and has been reported to suppress ras-dependent signaling. However, the mechanisms by which sulindac sulfone suppresses cancer growth are not as defined. We studied the effects of these sulindac metabolites in human colon cancer-derived Caco-2 cells that have been transfected with an activated K-ras oncogene. Stable transfected clones expressed high levels of COX-2 mRNA and protein, compared with parental cells. K-ras-transfected cells formed tumors more quickly when injected into severe combined immunodeficiency disease mice than parental cells, and this tumorigenesis was suppressed by treatment with sulindac. Sulindac sulfone inhibited COX-2 protein expression, which resulted in a decrease in prostaglandin synthase E2 production. Sulindac sulfide had little effect on COX-2 in this model, but did suppress prostaglandin synthase E2 production, presumably by inhibiting COX enzyme activity. These data indicate that the sulfide and sulfone derivatives of sulindac exert COX-dependent effects by distinct mechanisms.

Original languageEnglish (US)
Pages (from-to)6607-6610
Number of pages4
JournalCancer Research
Volume60
Issue number23
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Taylor, M. T., Lawson, K. R., Ignatenko, N. A., Marek, S. E., Stringer, D. E., Skovan, B. A., & Gerner, E. W. (2000). Sulindac sulfone inhibits K-ras-dependent cyclooxygenase-2 expression in human colon cancer cells. Cancer Research, 60(23), 6607-6610.