Ajit K Verma
University of Wisconsin, USA
Title: Topically applied Hsp90 inhibitor 17AAG inhibits ultraviolet radiation induced cutaneous wrinkles and squamous cell carcinomas
Biography
Biography: Ajit K Verma
Abstract
We present here that Heat shock protein 90ï¢ (Hsp90ï¢) interacts with protein kinase Cï¥ (PKCï¥); a predictive biomarker of various human cancers including ultraviolet radiation (UVR) induced cutaneous squamous cell carcinoma (SCC). Hsp90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17AAG), when topically applied to mouse skin, inhibits ultraviolet radiation (UVR) induced Hsp90ï¢-PKCï¥ interaction, wrinkle formation and development of SCC. In these experiments, DMSO:Acetone (1:40 v/v) solution of 17AAG (500 nmol) was applied topically to mouse skin in conjunction with each UVR exposure (1.8 kJ/m2). The UVR source was Kodacel-filtered FS-40 sun lamps (approximately 60% UVB and 40% UVA). In independent experiments with three separate mouse lines (wild-type FVB, PKCï¥ over expressing transgenic FVB and SKH-1 hairless mice), 17AAG treatment increased the latency and decreased both the incidence and multiplicity of UVR induced SCC. Topical 17AAG did not elicit any toxic effects. 17AAG caused inhibition of SCC induction accompanied decrease in UVR-induced: Hyperplasia, wrinkle formation and Hsp90ï¢-PKCε interaction, Hsp90ï¢, PKCε, Stat3, pStat3Ser727, pStat3Tyr705, Akt, pAktser473 and matrix metalloproteinase (MMPs) expression levels. The results presented here indicate that topical Hsp90 inhibitor 17AAG is nontoxic and is effective in prevention of epidermal hyperplasia, wrinkle formation and SCC.
