Uncovering the Anticancer Mechanism of Compound Sophorae Decoction against Ulcerative Colitis-Related Colorectal Cancer in Mice

• Main Authors: Shuangjiao Deng, Qing Tang, Xueyun Duan, Heng Fan, Lijuan Zhang, Xiwen Zhu, Jianli Hu, Meng Xu, Qianyun Chen, Yujin Liu, Yalan Dong, Zhen Nan, Hui Wu
• Format: Article
• Language: English
• Published: Hindawi Limited 2019-01-01
• Series: Evidence-Based Complementary and Alternative Medicine
• Online Access: http://dx.doi.org/10.1155/2019/8128170

Compound sophorae decoction (CSD), a traditional Chinese medicine (TCM) formula, has been voluminously used in China to deal with ulcerative colitis and gained significant therapeutic effect. Tremendous explorations have unraveled a contributory role of inflammatory bowel disease (IBD) like ulcerative colitis (UC) and Crohn’s disease (CD) at the onset of colorectal cancer, scilicet, and colitis-related cancer (CRC). In light of the anti-inflammatory properties of CSD in UC, we appraised its chemoprevention capacity and underlying mechanism in ulcerative colitis-related colorectal cancer (UCRCC), employing a model of azoxymethane (AOM) plus dextran sulfate sodium- (DSS-) induced colorectal cancer (CRC) in C57BL/6 mice. Rapturously, our results illuminated the ameliorative effect of CSD against UCRCC in mice portrayed by lesser polyps or adenomas, attenuated colonic xenograft tumor growth in company with the preferable well-being of mice in contrast to the Model Group. We examined significant downregulation of proinflammatory cytokines such as TNF-α, NF-κB, IL-6, STAT3, and IL-17 after exposure to CSD, with the concomitant repression of inflammation-associated proteins, including COX-2 and iNOS. Independent of this, treatment with CSD declined the proportion of T helper 17 cells (Th17) and protein level of matrix metallopeptidase 9 (MMP-9). Moreover, transmission electron microscopy (TEM) detected observably suppressed mitophagy in mice administered with CSD and that was paralleled by the pro-apoptotic effect as indicated by upregulating caspase-3 together with caspase-9 and deregulating B-cell lymphoma 2 (Bcl-2). In closing, these findings suggest CSD executes the UCRCC-inhibitory activity through counteracting inflammatory responses and rescuing detuning of apoptosis as well as neutralizing overactive mitophagy, concurring to build up an oncosuppressive microenvironment.