A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth.

ABSTRACT:

Background

This study investigates whether a histone deacetylase subtype 6 (HDAC6) inhibitor could be used in the treatment of solid tumours.

Methods

We evaluated the effect of a novel inhibitor, C1A, on HDAC6 biochemical activity and cell growth. We further examined potential of early noninvasive imaging of cell proliferation by [(18)F]fluorothymidine positron emission tomography ([(18)F]FLT-PET) to detect therapy response.

Results

C1A induced sustained acetylation of HDAC6 substrates, α-tubulin and HSP90, compared with current clinically approved HDAC inhibitor SAHA. C1A induced apoptosis and inhibited proliferation of a panel of human tumour cell lines from different origins in the low micromolar range. Systemic administration of the drug inhibited the growth of co

SUBMITTER: Kaliszczak M 

PROVIDER: S-EPMC3566806 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature