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.