| Targeting X-linked inhibitor of apoptosis protein to increase the efficacy of endoplasmic reticulum stress-induced apoptosis for melanoma therapy. | |
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MedLine Citation:
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PMID: 20520630 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Melanoma remains notoriously resistant to current chemotherapeutics, leaving an acute need for novel therapeutic approaches. The aim of this study was to determine the prognostic and therapeutic significance of X-linked inhibitor of apoptosis protein (XIAP) in melanoma through correlation of XIAP expression with disease stage, RAS/RAF mutational status, clinical outcome, and susceptibility to endoplasmic reticulum (ER) stress-induced cell death. XIAP expression and N-RAS/B-RAF mutational status were retrospectively determined in a cohort of 55 primary cutaneous melanocytic lesions selected and grouped according to the American Joint Committee on Cancer staging system. Short hairpin RNA interference of XIAP was used to analyze the effect of XIAP expression on ER stress-induced apoptosis in response to fenretinide or bortezomib in vitro. The results showed that XIAP positivity increased with progressive disease stage, although there was no significant correlation between XIAP positivity and combined N-RAS/B-RAF mutational status or clinical outcome. However, XIAP knockdown significantly increased ER stress-induced apoptosis of melanoma cells in a caspase-dependant manner. The correlation of XIAP expression with disease stage, as well as data showing that XIAP knockdown significantly increases fenretinide and bortezomib-induced apoptosis of metastatic melanoma cells, suggests that XIAP may prove to be an effective therapeutic target for melanoma therapy. |
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Authors:
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Emma L Hiscutt; David S Hill; Shaun Martin; Ryan Kerr; Andrew Harbottle; Mark Birch-Machin; Christopher P F Redfern; Simone Fulda; Jane L Armstrong; Penny E Lovat |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-03 |
Journal Detail:
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Title: The Journal of investigative dermatology Volume: 130 ISSN: 1523-1747 ISO Abbreviation: J. Invest. Dermatol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-16 Completed Date: 2010-09-16 Revised Date: 2012-06-21 |
Medline Journal Info:
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Nlm Unique ID: 0426720 Medline TA: J Invest Dermatol Country: United States |
Other Details:
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Languages: eng Pagination: 2250-8 Citation Subset: IM |
Affiliation:
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Dermatological Sciences, Institute of Cellular Medicine, Newcastle upon Tyne, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Apoptosis / drug effects, physiology Boronic Acids / pharmacology* Drug Resistance, Neoplasm Endoplasmic Reticulum / physiology Female Fenretinide / pharmacology* Gene Expression Regulation, Neoplastic Genes, ras / physiology Humans Male Melanoma / drug therapy*, metabolism, pathology Middle Aged Mutation / genetics Nevus, Pigmented / drug therapy, metabolism, pathology Proto-Oncogene Proteins B-raf / genetics Pyrazines / pharmacology* RNA, Small Interfering Skin Neoplasms / drug therapy*, metabolism, pathology Stress, Physiological / physiology X-Linked Inhibitor of Apoptosis Protein / antagonists & inhibitors*, genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Boronic Acids; 0/Pyrazines; 0/RNA, Small Interfering; 0/X-Linked Inhibitor of Apoptosis Protein; 0/XIAP protein, human; 0/bortezomib; 65646-68-6/Fenretinide; EC 2.7.11.1/BRAF protein, human; EC 2.7.11.1/Proto-Oncogene Proteins B-raf |
| Comments/Corrections | |
Comment In:
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J Invest Dermatol. 2010 Sep;130(9):2169-72
[PMID:
20711206
]
J Invest Dermatol. 2011 Mar;131(3):797 [PMID: 21068753 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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