Short-chain fatty acids administration is protective in colitis-associated colorectal cancer development |
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| Institution: | 1. Department of Oncology, Shanghai Dermatology Hospital, Tongji University, Shanghai 200443, China;2. Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, PR China;3. Tongji University Cancer Center, The Shanghai Tenth People''s Hospital, Tongji University, Shanghai, China;4. Department of Intensive Care Unit, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China;5. Emergency Center, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, PR China;6. Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, PR China;1. School of Pharmaceutical Sciences, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan;2. Cancer Prevention Laboratories, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan;3. Department of Diagnostic Pathology and Research Center of Diagnostic Pathology, Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu 500 8513, Japan;4. Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-cho, Hirosaki, Aomori 036-8561, Japan;5. Laboratory of Biofunctional Material Chemistry, Division of Marine Bioscience, Graduate School of Fisheries Sciences, Hokkaido University, Hakodate, Hokkaido 041-8611, Japan;6. Epidemiology and Preventions Group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan;1. Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, Georgia 30912, USA;2. Cancer Research Center, Augusta University, Augusta, Georgia 30912, USA;1. Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia;2. Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia;3. Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;4. Department of Biochemistry, Central Leather Research Institute, Council of Scientific and Industrial Research (CSIR), Adyar, Chennai 600 020, India |
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| Abstract: | Reduced short-chain fatty acids (SCFAs) have been reported in patients with ulcerative colitis, and increased intake of dietary fiber has shown to be clinically beneficial for colitis. Whether SCFAs suppress tumorigenesis in colitis-associated colorectal cancer remains unknown. The chemopreventive effect of SCFAs in colitis-associated colorectal cancer was evaluated in this study. Model of colitis-associated colorectal cancer in male BALB/c mice was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). SCFAs mix (67.5 mM acetate, 40 mM butyrate, 25.9 mM propionate) was administered in drink water during the study period. Macroscopic and histological studies were performed to examine the colorectal inflammation and tumorigenesis in AOM/DSS-induced mice treated with or without SCFA mix. The effects of SCFAs mix on colonic epithelial cellular proliferation were also assessed using Ki67 immunohistochemistry and TUNEL staining. The administration of SCFAs mix significantly reduced the tumor incidence and size in mice with AOM/DSS-induced colitis associated colorectal cancer. SCFAs mix protected from AOM/DSS-induced colorectal cancer by improving colon inflammation and disease activity index score as well as suppressing the expression of proinflammatory cytokines including IL-6, TNF-α and IL-17. A decrease in cell proliferation markers and an increase in TUNEL-positive tumor epithelial cells were also demonstrated in AOM/DSS mice treated with SCFAs mix. SCFAs mix administration prevented development of tumor and attenuated the colonic inflammation in a mouse model of colitis-associated colorectal cancer. SCFAs mix may be a potential agent in the prevention and treatment of colitis-associated colorectal cancer. |
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