Progesterone receptor chaperone complex-based high-throughput screening assay: Identification of capsaicin as an inhibitor of the Hsp90 machine

Chaitanya A. Patwardhan, Eyad Alfa, Su Lu, Ahmed Chadli

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Hsp90 and its co-chaperones are known to be important for cancer cell survival. The N-terminal inhibitors of Hsp90 that are in ongoing clinical trials as antitumor agents have unfortunately shown disappointing efficacies in the clinic. Thus, novel inhibitors of the Hsp90 machine with a different mechanism of action are urgently needed. 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.

Original languageEnglish (US)
Pages (from-to)223-229
Number of pages7
JournalJournal of Biomolecular Screening
Volume20
Issue number2
DOIs
StatePublished - Feb 24 2015

Fingerprint

High-Throughput Screening Assays
Capsaicin
Progesterone Receptors
Assays
Screening
Throughput
Cells
Cell Survival
Molecules
National Institutes of Health (U.S.)
United States Food and Drug Administration
Pain Management
Pharmaceutical Preparations
Antineoplastic Agents
Neoplasms
Health
Clinical Trials
Proteins

Keywords

  • Hsp90 machine
  • capsaicin
  • high-throughput screening assay
  • molecular chaperones
  • progesterone receptor

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Medicine
  • Biotechnology
  • Medicine(all)

Cite this

Progesterone receptor chaperone complex-based high-throughput screening assay : Identification of capsaicin as an inhibitor of the Hsp90 machine. / Patwardhan, Chaitanya A.; Alfa, Eyad; Lu, Su; Chadli, Ahmed.

In: Journal of Biomolecular Screening, Vol. 20, No. 2, 24.02.2015, p. 223-229.

Research output: Contribution to journalArticle

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