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Melatonin suppresses AOM/DSS-induced large bowel oncogenesis in rats |
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| Authors: | Takuji Tanaka Yumiko Yasui Takahiro Tanaka KM Wahidur Rahman |
| Affiliation: | a Department of Oncologic Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan b Department of Pharmacy, Kinjo Gakuin University of Pharmacy, 2-17723 Omori, Moriyama-ku, Aich 463-8521, Japan c Department of Physical Therapy, Kansai University of Health Sciences, 2-11-1 Wakaba, Kumatori-machi, Sennan-gun, Osaka 590-0482, Japan d Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, 9374 Scott Hall, 540 East Canfield, Detroit, MI 48201, USA |
| Abstract: | The inhibitory effects of exogenous melatonin (MEL) on colon oncogenesis were investigated using an azoxymethane (AOM)/dextran sodium sulfate (DSS) rat model. Male F344 rats initiated with a single intraperitoneal injection of AOM (20 mg/kg bw) were promoted by 1% (w/v) DSS in drinking water for 7 days. They were then given 0.4, 2 or 10 ppm MEL in drinking water for 17 weeks. At week 20, the development of colonic adenocarcinoma was significantly inhibited by the administration with MEL dose-dependently. MEL exposure modulated the mitotic and apoptotic indices in the colonic adenocarcinomas that developed and lowered the immunohistochemical expression of nuclear factor kappa B, tumor necrosis factor α, interleukin-1β and STAT3 in the epithelial malignancies. These results may indicate the beneficial effects of MEL on colitis-related colon carcinogenesis and a potential application for inhibiting colorectal cancer development in the inflamed colon. |
| Keywords: | ALT, alanine aminotransferase AOM, azoxymethane AST, aspartate aminotransferase COX, cyclooxygenase CRC, colorectal cancer DSS, dextran sodium sulfate dUTP, deoxyuridine triphosphate H & E, hematoxylin and eosin HDL, high-density lipoprotein IBD, inflammatory bowel disease IL, interleukin iNOS, inducible nitric oxide LDL, low-density lipoprotein MEL, melatonin MI, mitotic index NF-κB, nuclear factor-kappa B PCNA, proliferative cell nuclear antigen SNC, suprachiasmatic nuclei ssDNA, single stranded DNA T-Cho, total cholesterol TdT, terminal deoxynucleotidyl transferase TG, triglycerides TNF, tumor necrosis factor TUNEL, TdT-mediated dUTP-biotin nick end labeling VLDL, very low-density lipoprotein |
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