Inhibition of phenolsulphotransferase by salicylic acid: A possible mechanism by which aspirin may reduce carcinogenesis

Abstract

Background - Recent epidemiological evidence has shown that chronic use of aspirin decreases susceptibility to bowel cancer. Animal studies have shown that sulphotransferase inhibitors coadministered with sulphation activated carcinogens dramatically reduce the incidence of cancer. Aims - To investigate the effect of the main aspirin breakdown products salicylic acids on the P and M isoforms of phenolsulphotransferase from human platelets and colonic mucosa. Methods - Platelets were obtained from healthy blood donors and isolated within 24 hours after donation. Samples of colonic mucosa were obtained at resection for non-malignant disease. Phenolsulphotransferase activity was measured in cellular homogenates using a standard radiolabelling assay. Results - Salicylic acid consistently and selectively inhibited the P form of phenolsulphotransferase at subtherapeutic concentrations in both tissue samples. A 50% inhibition of sulphation by the P phenolsulphotransferase occurred at salicylic acid concentrations of about 40 and 130 μM in platelets and bowel mucosa respectively. M phenolsulphotransferase was virtually unaffected by salicylic acid up to a concentration of 1.5 mM (the therapeutic plasma concentration for salicylates when treating rheumatoid arthritis is about 1-2 mM). Conclusion - The action of salicylic acid on P phenolsulphotransferase, by preventing the excessive activation of carcinogens, is a possible additional pathway by which aspirin can reduce cancer risk.