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

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

Research output: Contribution to journalArticle

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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

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Cyclooxygenase 2
Colonic Neoplasms
Prostaglandin-Endoperoxide Synthases
Sulindac
Sulfides
Anticarcinogenic Agents
Severe Combined Immunodeficiency
Caco-2 Cells
ras Genes
Enzymes
Neoplasms
Carcinogenesis
Proteins
Anti-Inflammatory Agents
Theoretical Models
Clone Cells
Messenger RNA
sulindac sulfone
Growth
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Taylor, M. T., Lawson, K. R., Ignatenko, N., 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.

Sulindac sulfone inhibits K-ras-dependent cyclooxygenase-2 expression in human colon cancer cells. / Taylor, M. T.; Lawson, K. R.; Ignatenko, Natalia; Marek, S. E.; Stringer, D. E.; Skovan, B. A.; Gerner, E. W.

In: Cancer Research, Vol. 60, No. 23, 01.12.2000, p. 6607-6610.

Research output: Contribution to journalArticle

Taylor, MT, Lawson, KR, Ignatenko, N, Marek, SE, Stringer, DE, Skovan, BA & Gerner, EW 2000, 'Sulindac sulfone inhibits K-ras-dependent cyclooxygenase-2 expression in human colon cancer cells', Cancer Research, vol. 60, no. 23, pp. 6607-6610.
Taylor MT, Lawson KR, Ignatenko N, Marek SE, Stringer DE, Skovan BA et al. Sulindac sulfone inhibits K-ras-dependent cyclooxygenase-2 expression in human colon cancer cells. Cancer Research. 2000 Dec 1;60(23):6607-6610.
Taylor, M. T. ; Lawson, K. R. ; Ignatenko, Natalia ; Marek, S. E. ; Stringer, D. E. ; Skovan, B. A. ; Gerner, E. W. / Sulindac sulfone inhibits K-ras-dependent cyclooxygenase-2 expression in human colon cancer cells. In: Cancer Research. 2000 ; Vol. 60, No. 23. pp. 6607-6610.
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