Original Article
Copyright ©2010 Baishideng. All rights reserved
World J Gastroenterol. Mar 28, 2010; 16(12): 1473-1481
Published online Mar 28, 2010. doi: 10.3748/wjg.v16.i12.1473
Melatonin and Doxorubicin synergistically induce cell apoptosis in human hepatoma cell lines
Lu-Lu Fan, Guo-Ping Sun, Wei Wei, Zhang-Gui Wang, Lei Ge, Wei-Zheng Fu, Hua Wang
Lu-Lu Fan, Guo-Ping Sun, Zhang-Gui Wang, Lei Ge, Wei-Zheng Fu, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China
Wei Wei, Key Laboratory of Anti-inflammatory and Immunological Pharmacology, Key Laboratory of Research and Development of Chinese Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, Anhui Province, China
Hua Wang, Department of Oncology, The Affiliated Provincial Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China
Author contributions: Fan LL performed the majority of experiments and wrote the manuscript; Sun GP, Wang H and Wei W designed the study and were involved in revising the manuscript; Wang ZG, Ge L and Fu WZ provided the vital reagents and analytical tools.
Correspondence to: Dr. Guo-Ping Sun, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China. sunguoping@ahmu.edu.cn
Telephone: +86-551-2922354 Fax: +86-551-5161208
Received: December 10, 2009
Revised: January 12, 2010
Accepted: January 19, 2010
Published online: March 28, 2010
Abstract

AIM: To investigate whether Melatonin has synergistic effects with Doxorubicin in the growth-inhibition and apoptosis-induction of human hepatoma cell lines HepG2 and Bel-7402.

METHODS: The synergism of Melatonin and Doxorubicin inhibited the cell growth and induced cell apoptosis in human hepatoma cell lines HepG2 and Bel-7402. Cell viability was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Cell apoptosis was evaluated using TUNEL method and flow cytometry. Apoptosis-related protein Bax, Bcl-2 and caspase-3 expressions were measured by immunohistochemical staining.

RESULTS: Treatment with Melatonin (10-8-10-5 mol/L) alone had a dose-related inhibitory effect on cell proliferation but no cytotoxic effect on hepatoma cell lines HepG2 and Bel-7402. Interestingly, when combined with Doxorubicin, Melatonin significantly increased the effects of cell growth inhibition and cell apoptosis. Furthermore, TUNEL staining and flow cytometry revealed that cooperative apoptosis induction was associated with decreased expression of Bcl-2 as well as increased expression of Bax and Caspase3.

CONCLUSION: The synergism of Melatonin and Doxorubicin inhibits hepatoma cell growth and induces cell apoptosis.

Keywords: Melatonin; Doxorubicin; Human hepatoma cell line; Apoptosis