期刊
JOURNAL OF PINEAL RESEARCH
卷 55, 期 3, 页码 257-266出版社
WILEY
DOI: 10.1111/jpi.12068
关键词
apoptosis pathways; cholangiocarcinoma; melatonin; mitochondrial structure; Opisthorchis viverrini
资金
- Thailand Research Fund through Royal Golden Jubilee Ph.D. Program
- Thailand Research Fund [RMU5380016]
- Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, through the Health Cluster (SHeP-GMS), Khon Kaen University
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 (10mg/kg and 50mg/kg) for 120days. Melatonin treatment at 50mg/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.
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