title: Melatonin inhibits cholangiocarcinoma and reduces liver injury in Opisthorchis viverrini-infected and N-nitrosodimethylamine-treated hamsters.
abstract: The human liver fluke Opisthorchis viverrini infection and N-nitrosodimethylamine (NDMA) administration induce cholangiocarcinoma (CCA) and liver injury in hamsters. Melatonin protects against liver injury and reduces the alteration of mitochondrial structure, mitochondrial membrane potential, and mitochondrial pro- and anti-apoptotic pathways in various cancer types. To investigate the chemopreventive effect of melatonin on CCA genesis and liver injury, hamsters were treated with a combination of O. viverrini infection and NDMA concurrently administered with melatonin (10 mg/kg and 50 mg/kg) for 120 days. Melatonin treatment at 50 mg/kg caused a significant reduction in liver/body weight ratios and decreased tumor volumes leading to an increase in the survival of animals. In the tumorous tissues, the high-dose melatonin reduced DNA fragmentation and mitochondrial apoptosis by inducing anti-apoptotic protein (Bcl-2) in the mitochondrial fraction and down-regulating cytochrome c, pro-apoptotic protein (Bax), and caspase-3 in tumor cytosol. Moreover, a high-dose melatonin treatment significantly increased mitochondrial antioxidant enzymes and prevented mitochondrial ultrastructure changes in the tumor. Overall, melatonin has potent chemopreventive effects in inhibiting CCA genesis and also reduces liver injury in hamster CCA, which, in part, might involve in the suppression of CCA by reducing tumor mitochondria alteration.
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Umawadee
authors.initials: U
authors.lastname: Laothong
authors.forename: Porntip
authors.initials: P
authors.lastname: Pinlaor
authors.forename: Patcharee
authors.initials: P
authors.lastname: Boonsiri
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.forename: Aroonsri
authors.initials: A
authors.lastname: Priprem
authors.forename: Nutjaree Pratheepawanit
authors.initials: NP
authors.lastname: Johns
authors.forename: Lakhanawan
authors.initials: L
authors.lastname: Charoensuk
authors.forename: Kitti
authors.initials: K
authors.lastname: Intuyod
authors.forename: Somchai
authors.initials: S
authors.lastname: Pinlaor
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D018281:Cholangiocarcinoma / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control* / Q000648:ultrastructure; D006224:Cricetinae; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000633:toxicity; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control* / Q000648:ultrastructure; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008647:Mesocricetus; D008930:Mitochondria, Liver / Q000378:metabolism / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000378:metabolism; D009889:Opisthorchiasis / Q000150:complications; D009891:Opisthorchis; D013997:Time Factors
chemical_list: D000975:Antioxidants; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D008550:Melatonin; D004128:Dimethylnitrosamine
keywords: Opisthorchis viverrini; apoptosis pathways; cholangiocarcinoma; melatonin; mitochondrial structure