1541 Effects of TRPV1 Agonists/Antagonists on OSCC are Independent of TRPV1 Interactions

Saturday, March 24, 2012: 9:45 a.m. - 11 a.m.
Presentation Type: Poster Session
M. KUSBEL, J. DE LA CHAPA, and C. GONZALES, Comprehensive Dentistry, University of Texas - San Antonio / Health Science Ctr, San Antonio, TX
Oral Squamous Cell Carcinoma (OSCC) is the 8th most common cancer in the United States and has a high degree of morbidity and mortality. Consequently, 50% of all OSCC patients die from their disease.  Therefore, pain management is a primary concern for these patients. Previous research demonstrated the presence of Transient Receptor Potential (TRP) channels, not only in pain sensing neurons, but also in a number of tumor types.  Our laboratory demonstrated increased expression of TRP subfamily V member 1 (TRPV1) in numerous OSCC cell lines compared to normal oral keratinocytes.  Many authors hypothesize that TRP agonists may be used therapeutically through activating TRP channels resulting in high Ca++ influx and subsequent apoptosis. However, a number of studies demonstrate that while capsaicin is effective in reducing cancer cell proliferation, its antagonist capzasepine does not reverse this effect.  In fact, treatment with capzasepine alone results in a more significant reduction in cell proliferation. This implies that perhaps these drugs are working independent of TRP channels. Objective: To knock down the expression of TRPV1 in OSCC cells using siRNA and determine if treatment with TRPV1 agonists/antagonists results in reduced cell proliferation in absence of TRPV1 expression.  Methods: Previously characterized OSCC cell lines were transfected with TRPV1 siRNA to knock down TRPV1 expression. Negative (scramble) controls were also included.  The relative level of TRPV1 knock down was quantified against the housekeeping gene Cyclophilin A via Q-PCR. Cell viability after treatment with TRPV1 agonist and/or antagonist was determined by cell proliferation assays. Results: Treatment with capsaicin and/or capzasepine following 70% knock down of TRPV1 were both effective in reducing cell proliferation however capzasepine was significantly more effective (p<0.001).  Conclusions: These findings indicate that the effects of TRPV1 agonists and antagonists in reducing OSCC cell viability are likely independent of TRPV1 interactions.
This abstract is based on research that was funded entirely or partially by an outside source: American Cancer Society

Keywords: Carcinogenesis and Therapeutics