金雀异黄酮通过抑制黄嘌呤氧化酶延缓结肠肿瘤发展

流行病学研究表明摄入大豆制品可以降低罹患结直肠癌的风险,可能是大豆中含有丰富的异黄酮类物质,金雀异黄酮(genistein)是其中的主要成分.最近的研究表明,在核酸分解代谢中,催化嘌呤产生尿酸和活性氧的黄嘌呤氧化酶(xanthine oxidase,XO)可促进肿瘤的发展.同时,黄酮类物质显示出对XO抑制的巨大潜力,为...

Genistein retard the progression of colitis-associated colorectal cancer by inhibiting xanthine oxidase

Epidemiological studies have shown that the consumption of soybeans can reduce the risk of colorectal cancer(CRC).It may be that soybeans are rich in isoflavones,and genistein is the main ingredient.On the other hand,xanthine oxidase is the main enzyme that catalyzes the production of uric acid and reactive oxygen from purine in nucleic acid catabolism.Recent studies have shown that xanthine oxidase promote the development of cancer.Flavonoids have shown great potential in inhibiting xanthine oxidase.In order to explore the influence of flavonoid inhibitors on the development of colon cancer,firstly,we screened xanthine oxidase inhibitors by HPLC in vitro,including twelve flavonoids and two phenolic acid compounds.The results showed that 100μmol/L genistein significantly inhibited the activity of xanthine oxidase and had a dose-dependent effect.Secondly,a mouse model of primary colorectal tumors induced by AOM/DSS was established,when 40 mg/kg genistein was administered to mice,the number of tumors in the colon of mice significantly reduced.Compared with the control group,the expression and activity of xanthine oxidase,the uric acid level,and the TNF-αlevel in the colon of the model group were significantly increased.Compared with the model group,the expression and activity of xanthine oxidase xanthine,uric acid level,and TNF-αlevel in the colon of the mice in the genistein group,were significantly reduced,and genistein also increased the GSH level in the colon.These results indicate that genistein can delay the development of colon tumors by inhibiting the activity of xanthine oxidase.