Fas-associated factor 1 is a negative regulator in capsaicin induced cancer cell apoptosis.
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.
Ghosh
Amiya K
AK
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, MC1601, Farmington, CT 06030-1601, USA.
Basu
Sreyashi
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D002211:Capsaicin / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D054333:Drug Partial Agonism; D004789:Enzyme Activation; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D004224:Diterpenes; C097186:Faf1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C468130:iodoresiniferatoxin; C505409:Casp3 protein, mouse; D053148:Caspase 3; D002211:Capsaicin