Figure legends
Figure 1: Chemical structure of mitotane enantiomers (A) and chemical reaction of mitotane via α- and β-hydroxylation (B). Legend: o,p′-DDD, mitotane or 1,1-(o,p′-dichlorodiphenyl)-2,2-dichoroethane; o,p′-DDE, 1,1-(o,p′- diclorodifenil)-2,2 dicloroetano, o,p’-DDAC, o,p’ dichlorodiphenyl acyl chloride; o,p′-DDA, 1,1-(o,p′-dichlorodiphenyl) acetic acid; α-OH, α-hydroxylation; β-OH, β-hydroxylation.
Figure 2: Mechanism underlying the antitumor and antisecretory effects of mitotane (DDD) on adrenal cells. Legend: ABCG1, ATP-binding cassette sub-family G member 1; ADP, adenosine diphosphate; ATP, adenosine triphosphate; Bax, BCL2 associated X apoptosis regulator; Bcl-2, B-cell lymphoma protein 2; CHOP, C/EBP homologous protein; CYP11A1, cytochrome P450 family 11 subfamily A member 1; CYP17A1, cytochrome P450 family 17 subfamily A member 1; CYP21A2, cytochrome P450 family 21 subfamily A member 2; CYP11B1, cytochrome P450 family 11 subfamily B member 1; Cyt c, cytochrome c; DDD, mitotane; ER, endoplasmic reticulum; eIF2α, eukaryotic initiation factor 2 α phosphorylation; FAD, flavin adenine dinucleotide; NADH, nicotinamide adenine dinucleotide; PERK, protein kinase R-like endoplasmic reticulum kinase; SOAT1, sterol O-acyltransferase 1; SREBF: sterol regulatory element-binding transcription factor 1. Symbols: activation, inhibition.
Figure 3: Steroidogenic pathway and mitotane (DDD) interaction with specific CYPs. Legend: CYP11A1, cytochrome P450 family 11 subfamily A member 1; CYP17A1, cytochrome P450 family 17 subfamily A member 1; CYP21A2, cytochrome P450 family 21 subfamily A member 2; CYP19A2, cytochrome P450 family 19 subfamily A member 2; CYP11B1, cytochrome P450 family 11 subfamily B member 1; CYP11B2, cytochrome P450 family 11 subfamily B member 2; DDD, mitotane; DHEA, dehydroepiandrosterone; HSD3B2, hydroxy-delta-5-steroid dehydrogenase 3 beta- and steroid delta-isomerase type 2; HSD173B, hydroxy-delta-5-steroid dehydrogenase 17 beta- and steroid delta-isomerase; SRD5A2, 3-oxo-5α-steroid 4-dehydrogenase 2; StAR, steroidogenic acute regulatory protein; 3β-OH, 3β-hydroxylation; 17β-OH: 17β-hydroxylation. Symbols: activation, inhibition.