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4-Hydroxybenzoic acid derivatives as HDAC6-specific inhibitors modulating microtubular structure and HSP90a chaperone activity against prostate cancer

Authors
Type
Published Article
Journal
Biochemical Pharmacology
0006-2952
Publisher
Elsevier
Publication Date
Volume
99
Pages
31–52
Identifiers
DOI: 10.1016/j.bcp.2015.11.005
Source
LBMCC
Keywords
  • Hdac Inhibitor
  • Prostate Cancer
  • Hdac6

Abstract

Histone deacetylase (HDAC)6 is a unique isoenzyme targeting specific substrates including a-tubulin and heat shock protein (HSP)90. HDAC6 is involved in protein trafficking and degradation, cell shape and migration. Deregulation of HDAC6 activity is associated with a variety of diseases including cancer leading to a growing interest for developing HDAC6 inhibitors. Here, we identified two new structurally related 4-hydroxybenzoic acids as selective HDAC6 inhibitors reducing proliferation, colony and spheroid formation as well as viability of prostate cancer cells. Both compounds strongly enhanced a-tubulin acetylation leading to remodeling of microtubular organization. Furthermore, 4-hydroxybenzoic acids decreased HSP90a regulation of the human androgen receptor in prostate cancer cells by increasing HSP90a acetylation levels. Collectively, our data support the potential of 4-hydroxybenzoic acid derivatives as HDAC6-specific inhibitors with anti-cancer properties.

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