Melatonin inhibits cholangiocarcinoma and reduces liver injury in Opisthorchis viverrini‐infected and N‐nitrosodimethylamine‐treated hamsters

Journal of Pineal Research - Tập 55 Số 3 - Trang 257-266 - 2013
Umawadee Laothong1,2, Porntip Pinlaor3,2, Patcharee Boonsiri4, Chawalit Pairojkul5,2, Aroonsri Priprem6, Nutjaree Pratheepawanit Johns7, Lakhanawan Charoensuk1,2, Kitti Intuyod8,1,2, Somchai Pinlaor1,2
1Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
2Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
3Centre for Research and Development in Medical Diagnostic Laboratory, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand
4Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
5Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
6Division of Pharmaceutical Technology, and Melatonin Research group Khon Kaen University, Khon Kaen, Thailand
7Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, and Melatonin Research group, Khon Kaen University, Khon Kaen, Thailand
8Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand

Tóm tắt

AbstractThe 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.

Từ khóa


Tài liệu tham khảo

IARC, 2012, Opisthorchis viverrini and Clonorchis sinensis, IARC Monogr Eval Carcinog Risks Hum, 100, 341

10.1016/S0140-6736(05)67530-7

10.1016/S0278-6915(99)00017-4

10.1016/j.parint.2011.06.011

10.1093/carcin/bgh157

10.1002/ijc.25266

Rabes HM, 1983, DNA alkylation and tumor induction in regenerating rat liver after cell cycle‐related continuous N‐nitrosodimethylamine infusion, J Natl Cancer Inst, 70, 193

10.1016/0168-8278(89)90160-8

10.1038/sj.onc.1206039

10.1016/j.mito.2004.07.027

10.1038/sj.onc.1207513

10.1002/mnfr.200800044

10.1113/eph8802503

10.1146/annurev.biochem.73.011303.073706

10.1016/S0163-7258(01)00159-0

10.1111/j.1600-079X.2011.00916.x

10.1111/jpi.12010

Tan DX, 1993, Melatonin: a potent endogenous hydroxyl radical scavenger, Endocr J, 1, 57

10.1111/j.1600-079X.2007.00488.x

10.1111/jpi.12004

10.1111/j.1600-079X.2008.00647.x

10.1111/jpi.12026

10.1158/0008-5472.CAN-06-1776

10.1111/j.1600-079X.2012.01006.x

10.1111/j.1600-079X.2010.00792.x

10.1126/science.281.5381.1309

10.1016/0003-9861(59)90090-6

10.2174/156652407779940495

10.1016/j.mito.2012.06.007

10.3109/10715762.2011.623700

10.1111/j.1600-079X.2005.00248.x

10.1111/j.0959-9673.2006.00474.x

10.1111/j.1600-079X.2007.00478.x

10.1200/JCO.2002.11.004

10.1152/ajpgi.00118.2011

10.1136/gut.2004.053850

10.1152/ajplung.00245.2005

10.1002/ijc.25656

10.1016/j.cell.2011.02.013

10.1158/1541-7786.MCR-05-0261

10.1016/0167-5699(94)90018-3

10.1046/j.1600-079X.2003.00092.x

10.1007/s10620-007-0195-5

10.1016/S0024-3205(99)00519-6

10.1111/j.1600-079X.2004.00181.x

10.1023/A:1005425213253

10.1034/j.1600-079X.2001.300201.x

10.1073/pnas.93.6.2557

10.1093/hmg/ddm371

10.1111/j.1600-079X.2012.01014.x

10.1177/1534735408322846

10.1186/bcr1031

10.1093/toxsci/50.2.271

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Journal of Pineal Research

Tập 55 Số 3

257-266

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