Protective Effects of Zerumbone on Colonic Tumorigenesis in Enterotoxigenic Bacteroides fragilis (ETBF)-Colonized AOM/DSS BALB/c Mice

Abstract

Chronic inflammation has been linked to colitis-associated colorectal cancer in humans. The human symbiont enterotoxigenic Bacteroides fragilis (ETBF), a pro-carcinogenic bacterium, has the potential to initiate and/or promote colorectal cancer. Antibiotic treatment of ETBF has shown promise in decreasing colonic polyp formation in murine models of colon cancer. However, there are no reported natural products that have shown efficacy in decreasing polyp burden. In this study, we investigated the chemopreventive effects of oral administration of zerumbone in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. Zerumbone significantly reduced the severity of disease activity index (DAI) scores as well as several parameters of colonic inflammation (i.e., colon weight, colon length, cecum weight and spleen weight). In addition, inflammation of the colon and cecum as well as hyperplasia was reduced. Zerumbone treatment significantly inhibited colonic polyp numbers and prevented macroadenoma progression. Taken together, these findings suggest that oral treatment with zerumbone inhibited ETBF-promoted colon carcinogenesis in mice indicating that zerumbone could be employed as a promising protective agent against ETBF-mediated colorectal cancer.

A systemic review of the role of enterotoxic Bacteroides fragilis in colorectal cancer

“…Thirty in vivo mouse studies were identified and included in the analysis [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] . 87% of these studies used the C57BL6 mouse strain (26 studies [38 , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [51] , [52] , [53] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] ), 10% used the BALB/c mouse strain (3 studies [54] , [55] , [56] ), and 3% used a germ free (GF) NIH mouse strain (...…”

Lactobacillus fermentum ZS09 Mediates Epithelial–Mesenchymal Transition (EMT) by Regulating the Transcriptional Activity of the Wnt/β-Catenin Signalling Pathway to Inhibit Colon Cancer Activity

“…The establishment of an AOM/DSSinduced animal model of colon cancer is simple and economical and has a high success rate. [17][18][19] This model can accurately replicate the characteristics of human colon cancer disease. This experiment required 13 weeks to establish a mouse model of colon cancer.…”

Tumorigenic bacteria in colorectal cancer: mechanisms and treatments

“…Berberine blocked the secretion of mucosal immune factors, IL-21, IL-22, IL-31, and CD40L in mice, and prevented changes in F. nucleatum -induced intracellular signaling pathways 120 . In another example, zerumbone, the main component of Zingiber zerumbet , has been reported to have antibacterial, antiinflammatory and antitumor activities, and has been shown to reduce ETBF-induced, intestinal inflammation-related CRC by altering the IL-17, β-catenin, Stat3, and NF-κB pathways 121 .…”