| Norcantharidin induces melanoma cell apoptosis through activation of TR3 dependent pathway. | |
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MedLine Citation:
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PMID: 22123174 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Norcantharidin (NCTD) has been reported to induce tumor cell apoptosis. However, the underlying mechanism behinds its antitumor effect remains elusive. We have previously shown that TR3 expression is significantly decreased in metastatic melanomas and involved in melanoma cell apoptosis. In this study, we showed that NCTD inhibited melanoma cell proliferation and induced apoptosis in a dose related manner. NCTD induced translocation of TR3 from nucleus to mitochondria where it co-localized with Bcl-2 in melanoma cells. NCTD also increased cytochome c release from mitochondria to the cytoplasm. These changes were accompanied by increased expression of Bax and cleaved caspase-3 along with decreased expression of Bcl2 and NF-κB2. The effects of NCTD were inhibited by knockdown of TR3 expression using TR3 specific shRNA in melanoma cells. Furthermore, NCTD significantly decreased tumor volume and improved survival of Tyr::CreER; BRAF(Ca/+); Pten(lox/lox) transgenic mice. Our data indicates that NCTD inhibits melanoma growth by inducing tumor cell apoptosis via activation of a TR3 dependent pathway. These results suggest that NCTD is a potential therapeutic agent for melanoma. |
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Authors:
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Shujing Liu; Hong Yu; Suresh M Kumar; James S Martin; Zhanyong Bing; Weiqi Sheng; Marcus Bosenberg; Xiaowei Xu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-12-01 |
Journal Detail:
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Title: Cancer biology & therapy Volume: 12 ISSN: 1555-8576 ISO Abbreviation: Cancer Biol. Ther. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2012-02-03 Completed Date: 2012-06-01 Revised Date: 2013-03-08 |
Medline Journal Info:
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Nlm Unique ID: 101137842 Medline TA: Cancer Biol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1005-14 Citation Subset: IM |
Affiliation:
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Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / pharmacology* Apoptosis / drug effects*, genetics Bicyclo Compounds, Heterocyclic / pharmacology* Cell Line, Tumor Cell Proliferation Humans Melanoma / genetics, metabolism*, mortality Mice Mice, Transgenic Mitochondria / metabolism Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics, metabolism* Protein Binding / drug effects Protein Transport / drug effects Proto-Oncogene Proteins c-bcl-2 / metabolism Signal Transduction / drug effects* Xenograft Model Antitumor Assays |
| Grant Support | |
ID/Acronym/Agency:
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AR-054593/AR/NIAMS NIH HHS; CA-093372/CA/NCI NIH HHS; CA-116103/CA/NCI NIH HHS; R01 AR054593/AR/NIAMS NIH HHS; R01 AR054593-01A2/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Bicyclo Compounds, Heterocyclic; 0/Nuclear Receptor Subfamily 4, Group A, Member 1; 0/Proto-Oncogene Proteins c-bcl-2; 5442-12-6/norcantharidin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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