ATR-101 inhibits cholesterol efflux and cortisol secretion by ATP-binding cassette transporters, causing cytotoxic cholesterol accumulation in adrenocortical carcinoma cells.

ABSTRACT:

Background and purpose

To further the development of new agents for the treatment of adrenocortical carcinoma (ACC), we characterized the molecular and cellular mechanisms of cytotoxicity by the adrenalytic compound ATR-101 (PD132301-02).

Experimental approach

We compared the effects of ATR-101, PD129337, and ABC transporter inhibitors on cholesterol accumulation and efflux, on cortisol secretion, on ATP levels, and on caspase activation in ACC-derived cell lines. We examined the effects of these compounds in combination with methyl-β-cyclodextrin or exogenous cholesterol to determine the roles of altered cholesterol levels in the effects of these compounds.

Key results

ATR-101 caused cholesterol accumulation, ATP depletion, and caspase activation within 30 minutes af

SUBMITTER: Burns VE 

PROVIDER: S-EPMC5595769 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature