Progesterone Receptor Chaperone Complex-Based High-Throughput Screening Assay: Identification of Capsaicin as an Inhibitor of the Hsp90 Machine

We report here the development of a novel high-throughput screening assay platform to identify small-molecule inhibitors of Hsp90 and its co-chaperones. This assay quantitatively measures the ability of Hsp90 and its co-chaperones to refold/protect the progesterone receptor, a physiological client of Hsp90, in a 96-well plate format. We screened the National Institutes of Health clinical collection drug library and identified capsaicin as a hit molecule. Capsaicin is a Food and Drug Administration–approved drug for topical use in pain management. Cell survival assays showed that capsaicin selectively kills cancer cells and destabilizes several Hsp90 client proteins. Thus, our data may explain the seemingly pleotropic effect of capsaicin.

Source: Journal of Biomolecular Screening - January 22, 2015 Category: Molecular Biology Authors: Patwardhan, C. A., Alfa, E., Lu, S., Chadli, A. Tags: Original Research Source Type: research