Allopurinol Suppresses Azoxymethane-Induced Colorectal Tumorigenesis in C57BL/KsJ-db/db Mice

Abstract

Obesity and related metabolic disorders, including chronic inflammation and enhanced oxidative stress, are closely associated with the development and progression of colorectal cancer. Previous epidemiological studies have demonstrated that increased serum uric acid is associated with the risk for various types of cancer, including colon cancer. This study examined the effects of a xanthine oxidase inhibitor allopurinol, widely used as a uric acid lowering medicine, on colorectal tumorigenesis in obese mice. Male C57BL/KsJ-db/db mice were injected with azoxymethane (15 mg/kg body weight) and then received drinking water containing allopurinol (30 mg/kg body weight) for fourteen weeks. At the time of sacrifice, allopurinol treatment significantly inhibited the development of colonic premalignant lesions. In the allopurinol-treated group, cellular proliferation in colonic mucosa was significantly suppressed, which was evaluated by the expression of proliferating cell nuclear antigen. Allopurinol also inhibited macrophage infiltration in the adipose tissue and decreased the serum level of TNF-α. The values of oxidative stress markers were markedly decreased in the allopurinol-treated group compared to those in the control group. These findings suggest that allopurinol attenuated chronic inflammation and decreased oxidative stress, preventing the development of colonic pre-neoplastic lesions in obesity-associated colon tumorigenesis model.