Cancer Research Center of Toulouse, UMR 1037 INSERM-University Toulouse III, Institut Claudius Regaud, Toulouse, France.
Curr Opin Pharmacol. 2012 Dec;12(6):696-703. doi: 10.1016/j.coph.2012.07.007. Epub 2012 Aug 21.
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.
胆固醇环氧化物水解酶（ChEH）催化胆固醇-5,6-环氧化物（5,6-EC）水合为胆甾烷-3β,5α,6β-三醇。ChEH 是一种称为抗雌激素结合位点（AEBS）的异型寡聚体复合物，由 3β-羟甾醇-Δ(8)-Δ(7)-异构酶（D8D7I）和 3β-羟甾醇-Δ(7)-还原酶（DHCR7）组成。D8D7I 和 DHCR7 调节胆固醇生物合成、胎儿发育和生长、肿瘤细胞分化和死亡。最近已经证明 5,6-EC 对亲核试剂没有反应性，这表明 5,6-EC 不是最初假设的烷化剂和致癌剂。在这里，我们讨论了 ChEH 的分子特征的最新进展、它在癌症进展和耐药性中的潜在作用，以及抑制 ChEH 和积累 5,6-EC 的兴趣，这可能有助于临床中使用的 ChEH 抑制剂（如他莫昔芬）的抗肿瘤和化学预防作用。
