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Evaluation of prostate-specific antigen as a novel biomarker of Hsp90 inhibition

Authors
Journal
Clinical Biochemistry
0009-9120
Publisher
Elsevier
Publication Date
Volume
42
Identifiers
DOI: 10.1016/j.clinbiochem.2009.07.018
Keywords
  • Androgen Receptor
  • Heat Shock Protein 90
  • Hsp90 Inhibitors
  • Human Kallikrein-Related Peptidase
  • Prostate-Specific Antigen
Disciplines
  • Biology
  • Medicine

Abstract

Abstract Objectives Hsp90 inhibition has already been evaluated by assessing the expression of proteins, like the androgen receptor (AR) and the IGFBP-2. We hypothesized that AR-regulated proteins, such as prostate-specific antigen (PSA), may serve as biomarkers for Hsp90 inhibition. Design and methods We utilized the androgen-stimulated BT-474 breast cancer cells to trigger PSA secretion, which was quantified by ELISA. PSA concentration was used to evaluate the potency of an experimental compound (NVP-AUY922), in comparison to the commercially available 17-allylamine-17-demethoxygeldanamycin (17-AAG) Hsp90 inhibitor. Results PSA concentration was reduced in a dose-dependent manner (2-fold more than IGFBP-2) and was accompanied by AR decrease. Utilizing PSA expression as a marker for Hsp90 inhibition, we concluded that the novel NVP-AUY922 inhibitor was about 8-fold more potent than 17-AAG. Conclusions This study showed that PSA may serve as a sensitive biomarker of Hsp90 inhibition and may aid in selecting new chemotherapeutics. Furthermore, the novel Hsp90 inhibitor was highly potent, suggesting that it may be an attractive agent for clinical trials.

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