Mitotane

Mitotane (2,4′-DDD), an isomer of DDD and derivative of dichlorodiphenyltrichloroethane (DDT), is an antineoplastic agent, can be used to research adrenocortical carcinoma. Mitotane exert its adrenocorticolytic effect at least in part through lipotoxicity induced by intracellular free cholesterol (FC) accumulation. Mitotane can have direct pituitary effects on corticotroph cells. Mitotane can induce CYP3A4 gene expression via steroid and xenobiotic receptor (SXR) activation, and has drug-drug interactions^[1][2][3][4]. IC50 & Target:Apoptosis^[1] In Vitro:Mitotane (1 nM-100 μM; 6 days) significantly reduces H295R cell proliferation^[1].
Mitotane (10-100 μM; 6 or 48 h; TαT1 cells) reduces TαT1 cell viability in time- and dose-dependent manners; significantly and dose dependently increases caspase 3/7 activity from 60 μM to 80 μM; induced a significant and dose-dependent reduction in TSH secretion and TSH β-subunit mRNA expression from 40 μM to 100 μM^[2].
Mitotane (1-30 μM; 24 h; HepG2) increases transcription of the CYP3A4 and CYP2B6 gene in a dose-dependent manner^[3].
Mitotane (20 and 40 μM; 6 h) significantly reduces the number of neutral lipid droplets per cell in HepaRG, also induces a significant decrease in triacylglycerol-labeled lipid droplets; decreases the expression levels of PLIN1 and PLIN3^[4]. In Vivo:Mitotane (440 mg/kg; i.p. or p.o,; 5 days a week, for 7 weeks) significantly reduces the volume of xenografts at an early time point after H295R cells inoculation^[1].