Differential growth inhibition by the aspirin metabolite salicylate in human colorectal tumor cell lines: enhanced apoptosis in carcinoma and in vitro-transformed adenoma relative to adenoma relative to adenoma cell lines.
Regular aspirin intake may reduce the risk of colorectal cancer by 50%. However, the mechanism of this chemopreventive effect is not known. The effect of the aspirin metabolite salicylate on the growth of human colorectal tumor cell lines was determined. Salicylate showed dose-dependent inhibitory effects on all of the cell lines (IC50, 1.65 +/- 0.36 to 7.38 +/- 1.08 mM), yet carcinoma and in vitro-transformed adenoma cell lines were more sensitive than adenoma cell lines. Salicylate caused all cell lines to accumulate in G0-G1 and induced apoptosis in carcinoma and in vitro-transformed adenoma cell lines but not in all adenoma cell lines. In those adenoma lines that did show salicylate-induced apoptosis, the extent was considerably less than that in the more transformed cell lines. The ability of salicylate to induce cell cycle arrest and apoptosis and, in particular, the increased sensitivity of cells at later stages of neoplastic progression may be mechanistically important in the chemopreventive action of aspirin toward colorectal cancer.
Elder
D J
DJ
Department of Pathology and Microbiology, Cancer Research Campaign Colorectal Tumor Biology Research Group, School of Medical Sciences, University of Bristol, United Kingdom.
Hague
A
A
Hicks
D J
DJ
Paraskeva
C
C
D016475:3T3 Cells; D000236:Adenoma / Q000473:pathology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000493:pharmacokinetics*; D002277:Carcinoma / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D015179:Colorectal Neoplasms / Q000473:pathology*; D006801:Humans; D051379:Mice; D012306:Risk; D012980:Sodium Salicylate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin; D012980:Sodium Salicylate