The 5,6-epoxycholesterol metabolic pathway in breast cancer: Emergence of new pharmacological targets.

Autor: de Medina P; UMR-1037, Cancer Research Center of Toulouse (CRCT), Team 'Cholesterol Metabolism and Therapeutic Innovations'; Equipe labellisée par la Ligue Nationale Contre le Cancer, The French Network for Nutrition and Cancer Research (NACRe Network), INSERM-Université de Toulouse, Toulouse, France., Diallo K; UMR-1037, Cancer Research Center of Toulouse (CRCT), Team 'Cholesterol Metabolism and Therapeutic Innovations'; Equipe labellisée par la Ligue Nationale Contre le Cancer, The French Network for Nutrition and Cancer Research (NACRe Network), INSERM-Université de Toulouse, Toulouse, France., Huc-Claustre E; UMR-1037, Cancer Research Center of Toulouse (CRCT), Team 'Cholesterol Metabolism and Therapeutic Innovations'; Equipe labellisée par la Ligue Nationale Contre le Cancer, The French Network for Nutrition and Cancer Research (NACRe Network), INSERM-Université de Toulouse, Toulouse, France., Attia M; UMR-1037, Cancer Research Center of Toulouse (CRCT), Team 'Cholesterol Metabolism and Therapeutic Innovations'; Equipe labellisée par la Ligue Nationale Contre le Cancer, The French Network for Nutrition and Cancer Research (NACRe Network), INSERM-Université de Toulouse, Toulouse, France., Soulès R; UMR-1037, Cancer Research Center of Toulouse (CRCT), Team 'Cholesterol Metabolism and Therapeutic Innovations'; Equipe labellisée par la Ligue Nationale Contre le Cancer, The French Network for Nutrition and Cancer Research (NACRe Network), INSERM-Université de Toulouse, Toulouse, France., Silvente-Poirot S; UMR-1037, Cancer Research Center of Toulouse (CRCT), Team 'Cholesterol Metabolism and Therapeutic Innovations'; Equipe labellisée par la Ligue Nationale Contre le Cancer, The French Network for Nutrition and Cancer Research (NACRe Network), INSERM-Université de Toulouse, Toulouse, France., Poirot M; UMR-1037, Cancer Research Center of Toulouse (CRCT), Team 'Cholesterol Metabolism and Therapeutic Innovations'; Equipe labellisée par la Ligue Nationale Contre le Cancer, The French Network for Nutrition and Cancer Research (NACRe Network), INSERM-Université de Toulouse, Toulouse, France.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2021 Aug; Vol. 178 (16), pp. 3248-3260. Date of Electronic Publication: 2020 Aug 23.
DOI: 10.1111/bph.15205
Abstrakt: Metabolic pathways have emerged as cornerstones in carcinogenic deregulation providing new therapeutic strategies for cancer management. Recently, a new branch of cholesterol metabolism has been discovered involving the biochemical transformation of 5,6-epoxycholesterols (5,6-ECs). The 5,6-ECs are metabolized in breast cancers to the tumour promoter oncosterone whereas, in normal breast tissue, they are metabolized to the tumour suppressor metabolite, dendrogenin A (DDA). Blocking the mitogenic and invasive potential of oncosterone will present new opportunities for breast cancer treatment. The reactivation of DDA biosynthesis, or its use as a drug, represents promising therapeutic approaches such as DDA-deficiency complementation, activation of breast cancer cell re-differentiation and breast cancer chemoprevention. This review presents current knowledge of the 5,6-EC metabolic pathway in breast cancer, focusing on the 5,6-EC metabolic enzymes ChEH and HSD11B2 and on 5,6-EC metabolite targets, the oxysterol receptor (LXRβ) and the glucocorticoid receptor. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.
(© 2020 The British Pharmacological Society.)
Databáze: MEDLINE
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