Soy Saponins Meditate the Progression of Colon Cancer in Rats by Inhibiting the Activity of β-Glucuronidase and the Number of Aberrant Crypt Foci but Not Cyclooxygenase-2 Activity
Objective. The effect of extracted crude soybean saponins on preneoplastic lesions, aberrant crypt foci (ACF), and the related mechanism were investigated. Research Methods and Procedures. Rats were assigned into five groups according to different doses of extracted crude soybean saponins and received 1,2-dimethylhydrazine (DMH) injection in week 5. In week 15, all rats were sacrificed. The number of ACFs, the cyclooxygenase-2 (COX-2) protein expression, the level of prostaglandins E2 (PGE2), and the activity of β-glucuronidase were examined. Results. Results revealed that the consumption of extracted crude soybean saponins decreased the number of ACFs and the activity of β-glucuronidase in rats, while the expression of COX-2 protein and PGE2 level were not affected. Conclusions. Soybean saponins were effective in inhibiting colon cancer by downregulating the activity of β-glucuronidase in colonic mucosa but not the COX-2 protein expression and PGE2 level. 1. Introduction Dietary habit is one of the major factors that cause colon cancer. It was reported that the colon cancer mortalities are higher in the countries where people consume more animal fat [1]. On the other hand, fiber-rich foods increase the volume of feces and promote the creeping motion of the large intestine, hence, reduce the contacting time of carcinogens in the body [2]. The development of tumor cells the early stage is closely related to inflammatory responses. Immune response factors such as cytokines, reactive oxygen species (ROS), proinflammatory enzyme cyclooxygenase-2 (COX-2), and nitric oxide synthase (iNOS) may accelerate the development of cancer [3]. It has been indicated that colon cancer progression could be slowed down by reducing the expression of COX-2 protein or reducing inflammatory reaction [4, 5]. At the location of inflammation, iNOS may cause the overproduction of nitric oxide, which results in damages on DNA repair and promotes the proliferation of cancer cells [6]. In the early stage of colon cancer in human, lowering the expression of iNOS could be used to reduce the formation of cancer cells [7]. In addition, carcinogens may increase the activities of COX-2 and iNOS on the mucosa of the colon, which also causes the promotion of cancer occurrence [7]. Both COX-2 and iNOS are upregulated by NF-κB. It was indicated that by reducing NF-κB expression, the occurrence of cancer can be reduced [8]. There are several enzymes other than immune response factors, such as nitroreductase, azoreductase, and -glucuronidase produced by the bacteria in the intestine, that are
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