Sulindac sulfide, but not sulindac sulfone, inhibits colorectal cancer growth.
Sulindac sulfide, a metabolite of the nonsteroidal antiinflammatory drug (NSAID) sulindac sulfoxide, is effective at reducing tumor burden in both familial adenomatous polyposis patients and in animals with colorectal cancer. Another sulindac sulfoxide metabolite, sulindac sulfone, has been reported to have antitumor properties without inhibiting cyclooxygenase activity. Here we report the effect of sulindac sulfone treatment on the growth of colorectal carcinoma cells. We observed that sulindac sulfide or sulfone treatment of HCA-7 cells led to inhibition of prostaglandin E2 production. Both sulindac sulfide and sulfone inhibited HCA-7 and HCT-116 cell growth in vitro. Sulindac sulfone had no effect on the growth of either HCA-7 or HCT-116 xenografts, whereas the sulfide derivative inhibited HCA-7 growth in vivo. Both sulindac sulfide and sulfone inhibited colon carcinoma cell growth and prostaglandin production in vitro, but sulindac sulfone had no effect on the growth of colon cancer cell xenografts in nude mice.
Department of Medicine, The Vanderbilt Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232-2279, USA.
C S
CS
Williams
A P
AP
Goldman
H
H
Sheng
J D
JD
Morrow
R N
RN
DuBois
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002849:Chromatography, Gas; D003094:Collagen; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004591:Electrophoresis, Polyacrylamide Gel; D007527:Isoenzymes / Q000378:metabolism; D007797:Laminin; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011509:Proteoglycans; D013467:Sulindac / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D004338:Drug Combinations; D007527:Isoenzymes; D007797:Laminin; D008565:Membrane Proteins; D011509:Proteoglycans; C059485:matrigel; D013467:Sulindac; C025462:sulindac sulfide; D003094:Collagen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; C025463:sulindac sulfone; D015232:Dinoprostone