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Mitotane Targets Lipid Droplets to Induce Lipolysis in Adrenocortical Carcinoma.


ABSTRACT:

Introduction

Adrenocortical carcinoma (ACC) is a rare aggressive cancer with low overall survival. Adjuvant mitotane improves survival but is limited by poor response rates and resistance. Mitotane's efficacy is attributed to the accumulation of toxic free cholesterol, predominantly through cholesterol storage inhibition. However, targeting this pathway has proven unsuccessful. We hypothesize that mitotane-induced free-cholesterol accumulation is also mediated through enhanced breakdown of lipid droplets.

Methodology

ATCC-H295R (mitotane-sensitive) and MUC-1 (mitotane-resistant) ACC cells were evaluated for lipid content using specific BODIPY dyes. Protein expression was evaluated by immunoblotting and flow cytometry. Cell viability was measured by quantifying propidium iodi

SUBMITTER: Warde KM 

PROVIDER: S-EPMC9342684 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature