| Melatonin sensitizes human hepatoma cells to endoplasmic reticulum stress-induced apoptosis. | |
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MedLine Citation:
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PMID: 22225575 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Endoplasmic reticulum stress-mediated cell apoptosis is implicated in the development of cancer. Melatonin induces apoptosis in hepatocellular carcinoma (HCC) in experimental studies, but the effects of melatonin on endoplasmic reticulum (ER) stress-induced apoptosis in HCC have not been tested. Differences in ER stress-induced apoptosis in human hepatoma cells and normal human hepatocyte were investigated by exposure to tunicamycin (ER stress inducer). Significant differences were observed in the rate of apoptosis between HepG2 cells (hepatoma cells) and HL-7702 cells (normal human hepatocyte cells). The expression of cyclooxygenase-2 (COX-2) was increased in HepG2 cells but not in HL-7702 cells. Furthermore, down-regulation of COX-2 expression using the COX-2 inhibitor, celecoxib, increased tunicamycin-induced apoptosis concomitant with the up-regulation of pro-apoptotic transcription factor CHOP (GADD153) and down-regulation of B-cell lymphoma 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, suggesting that inhibition of COX-2 sensitized human hepatoma cells to ER stress-induced apoptosis. Interestingly, co-treatment with tunicamycin and melatonin also decreased the expression of COX-2 and significantly increased the rate of apoptosis by elevating the levels of CHOP and reducing the Bcl-2/Bax ratio. These results demonstrate that melatonin sensitizes human hepatoma cells to ER stress-induced apoptosis by down-regulating COX-2 expression, increasing the levels of CHOP and decreasing the Bcl-2/Bax ratio. |
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Authors:
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Lixia Zha; Lulu Fan; Guoping Sun; Hua Wang; Tai Ma; Fei Zhong; Wei Wei |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-5 |
Journal Detail:
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Title: Journal of pineal research Volume: - ISSN: 1600-079X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2012-1-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8504412 Medline TA: J Pineal Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 John Wiley & Sons A/S. |
Affiliation:
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Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China Department of Oncology, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui, China Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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