| Fas-associated factor 1 is a negative regulator in capsaicin induced cancer cell apoptosis. | |
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MedLine Citation:
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PMID: 19570606 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Vanilloid receptor1 (VR1/TRPV1) is expressed on peripheral nerves and involved in sensing of temperature and pain. Recent reports have demonstrated that tumor cells express TRPV1 and that capsaicin (CP), a ligand for TRPV1, induces apoptosis in cancer cells. The mechanism underlying CP-induced tumor cell apoptosis remains unclear. Here, we investigated the role of TRPV1 in tumor apoptosis using TRPV1-expressing cancer cell lines. We demonstrate that iodo-resiniferatoxin (I-RTX), an antagonist of TRPV1 does not inhibit CP mediated apoptosis nor is it cytotoxic by itself, but acts as a partial agonist and shows synergistic effect with CP. We further demonstrate that CP treatment degrades Fas-associated factor1 (FAF1); a TRPV1 associated protein. Moreover, using RNA interference with small inhibitory RNAs (siRNA) for FAF1 we observed that down-regulation of FAF1 by siRNA makes the cell susceptible to enhanced apoptosis with CP. In summary, our data shows for the first time that the underlying mechanisms of CP-induced cancer cell apoptosis involves FAF1, a TRPV1 associated protein and serves as an important foundation for further understanding of anticancer activity of CP. |
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Authors:
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Amiya K Ghosh; Sreyashi Basu |
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Publication Detail:
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Type: Journal Article Date: 2009-06-30 |
Journal Detail:
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Title: Cancer letters Volume: 287 ISSN: 1872-7980 ISO Abbreviation: Cancer Lett. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-02-01 Completed Date: 2010-03-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 142-9 Citation Subset: IM |
Copyright Information:
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Published by Elsevier Ireland Ltd. |
Affiliation:
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Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, MC1601, Farmington, CT 06030-1601, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / pharmacology Apoptosis / drug effects* Capsaicin / pharmacology* Carrier Proteins / genetics, metabolism* Caspase 3 / metabolism Cell Line, Tumor Diterpenes / pharmacology Dose-Response Relationship, Drug Drug Partial Agonism Enzyme Activation Fibrosarcoma / metabolism, pathology* Mice Mice, Inbred BALB C RNA Interference RNA, Messenger / metabolism Reactive Oxygen Species / metabolism TRPV Cation Channels / agonists*, genetics, metabolism Time Factors Transfection |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Carrier Proteins; 0/Diterpenes; 0/Faf1 protein, mouse; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/TRPV Cation Channels; 0/TRPV1 protein, mouse; 0/iodoresiniferatoxin; 404-86-4/Capsaicin; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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