Cholesterol epoxide hydrolase and cancer.
Cholesterol epoxide hydrolase (ChEH) catalyzes the hydration of cholesterol-5,6-epoxides (5,6-EC) into cholestane-3β,5α,6β-triol. ChEH is a hetero-oligomeric complex called the anti-estrogen binding site (AEBS) comprising 3β-hydroxysterol-Δ(8)-Δ(7)-isomerase (D8D7I) and 3β-hydroxysterol-Δ(7)-reductase (DHCR7). D8D7I and DHCR7 regulate cholesterol biosynthesis, fetal development and growth, tumor cell differentiation and death. The un-reactivity of 5,6-EC toward nucleophiles has recently been demonstrated indicating that 5,6-EC are not alkylating and carcinogenic agents as first postulated. Here we discuss recent advances in the molecular characterization of ChEH, its potential role in cancer progression and resistance as well as the interest of inhibiting ChEH and to accumulate 5,6-EC which may contribute to the anti-tumor and chemopreventive action of ChEH inhibitors used in the clinic such as tamoxifen.
Cancer Research Center of Toulouse, UMR 1037 INSERM-University Toulouse III, Institut Claudius Regaud, Toulouse, France. poirot.sandrine@hotmail.fr
Sandrine
S
Silvente-Poirot
Marc
M
Poirot
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002777:Cholestanols / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D013629:Tamoxifen / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D002777:Cholestanols; D013629:Tamoxifen; C000474:cholestane-3,5,6-triol; C002415:cholesterol alpha-oxide; D002784:Cholesterol; D004851:Epoxide Hydrolases; C019885:cholesterol-5 alpha,6 alpha-epoxide hydrase