The HDAC6 inhibitor C1A modulates autophagy substrates in diverse cancer cells and induces cell death.

ABSTRACT:

Background

Cytosolic deacetylase histone deacetylase 6 (HDAC6) is involved in the autophagy degradation pathway of malformed proteins, an important survival mechanism in cancer cells. We evaluated modulation of autophagy-related proteins and cell death by the HDAC6-selective inhibitor C1A.

Methods

Autophagy substrates (light chain-3 (LC-3) and p62 proteins) and endoplasmic reticulum (ER) stress phenotype were determined. Caspase-3/7 activation and cellular proliferation assays were used to assess consequences of autophagy modulation.

Results

C1A potently resolved autophagy substrates induced by 3-methyladenine and chloroquine. The mechanism of autophagy inhibition by HDAC6 genetic knockout or C1A treatment was consistent with abrogation of autophagosome-lysosome fusio

SUBMITTER: Kaliszczak M 

PROVIDER: S-EPMC6251030 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature