PT  - JOURNAL ARTICLE
AU  - Taylor, Michele T.
AU  - Lawson, Kathryn R.
AU  - Ignatenko, Natalia A.
AU  - Marek, Sarah E.
AU  - Stringer, David E.
AU  - Skovan, Beth A.
AU  - Gerner, Eugene W.
TI  - Sulindac Sulfone Inhibits K-ras-dependent Cyclooxygenase-2 Expression in Human Colon Cancer Cells
DP  - 2000 Dec 01
TA  - Cancer Research
PG  - 6607--6610
VI  - 60
IP  - 23
4099  - http://cancerres.aacrjournals.org/content/60/23/6607.short
4100  - http://cancerres.aacrjournals.org/content/60/23/6607.full
SO  - Cancer Res2000 Dec 01; 60
AB  - 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. ©2000 American Association for Cancer Research.