Beta-glucuronidase system, intestinal microflora, and genesis of colorectal tumors

The review analyzes cellular and molecular aspects of the participation of intestinal microflora and related features of luminal metabolism in the occurrence and subsequent development of colon tumors, primarily colorectal cancer. The article describes the problems of increasing frequency of this disease in recent years, the participation of genetic factors in high risk of colorectal cancer progression. According to the authors, microbial associations and the consequences of the interaction between individual types of microorganisms are of importance. The role of the intestinal microflora can largely be reduced to the activity of its enzyme secretion, which changes the ratio of keymetabolites in the intestinal lumen and its permeability. These alterations affect the rate of metabolism and renewal of epithelial cells. From these positions, the structural features and biochemical characteristics of beta- glucuronidase, as a key enzyme involved in the carcinogenesis of colorectal cancer, are considered in detail. The main information about the role of beta-glucuronidase in the clearance of xenobiotics, physiological and pathological consequences of the activity of this enzyme in the intestinal lumen are given. Modern methods for determining the activity, isolation, and purification of beta-glucuronidase, including chromogenic substrate application, are briefly described. At the end of the review, the authors present several approaches based on the use of beta-glucuronidase for targeted delivery of therapeutic agents to the tumor, as an element of complex chemotherapy for colorectal cancer.