Cholesterol epoxide hydrolase and cancer
Abstract
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.
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TAM binding to ChEH inhibits the enzyme's activity, resulting in the accumulation of cholesterol-5,6-epoxides and the inhibition of cholestane-3β,5α,6β-triol production.
“TAM binding to ChEH inhibits the enzyme’s activity, resulting in the accumulation of cholesterol-5,6-epoxides and the inhibition of cholestane-3β,5α,6β-triol production [26].”
From Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis (2015) · cites this paper as [26]
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Pathogenic Role of 25-Hydroxycholesterol in Cancer Development and Progression
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27-hydroxylation of oncosterone by CYP27A1 switchs its activity from pro-tumor to anti-tumorPreprint
Ayadi, S., Friedrichs, S., Soulès, R., Pucheu, L., Lütjohann, D., Silvente‐Poirot, S., Poirot, M., & de Médina, P. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.10.560948
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- Authors
- Silvente-Poirot, S., & Poirot, M.
- Affiliations
- Inserm (FR)
- ORCID
- Poirot, Marc
- Venue
- Current Opinion in Pharmacology
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 12
- Issue
- 6
- Pages
- 696-703
- ISSN
- 1471-4892 (ISSN-L)
- OpenAlex
- W2154795264
- Cited by
- 82
- References
- 54
- Citations by year
- 2026: 7 · 2025: 2 · 2024: 5 · 2023: 12 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 9 · 2017: 4 · 2016: 8 · 2015: 4 · 2014: 2 · 2013: 6 · 2012: 1
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche
- Centre National de la Recherche Scientifique
- Institut National Du Cancer
- Institut Claudius Regaud
- Institute of Cancer Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- cholestane-3β,5α,6β-triol, DHCR7, cholesterol biosynthesis, tumor progression, chemoresistance, tamoxifen, chemoprevention, alkylating agents, tumor cell differentiation
- MeSH terms
- Animals, Cholestanols, Cholesterol, Epoxide Hydrolases, Humans, Neoplasms, Tamoxifen, Disease Progression, Antineoplastic Agents, Hormonal, Drug Resistance, Neoplasm
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