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The 5,6-epoxycholesterol metabolic pathway in cancer: emergence of new pharmacological targets

Abstract : Metabolic pathways have emerged as cornerstones in carcinogenic deregulation providing new therapeutic strategies for cancer management. This is illustrated by the recent discovery of a cholesterol metabolic branch involving the biochemical transformation of 5,6-epoxycholesterol (5,6-ECs). 5,6-ECs have been shown to be differentially metabolized in breast cancers (BC) compared to normal breast tissue. 5,6-ECs are metabolized into the tumour promoter oncosterone in BC, while they are transformed into the tumour suppressor metabolite dendrogenin A (DDA) in normal breast tissue. Blocking oncosterone’s mitogenic and invasive potential will represent new opportunities for BC treatment. The reactivation of DDA biosynthesis, or its use as a drug, represents promising therapeutic approaches such as DDA-deficiency complementation, activation of BC cell re-differentiation and BC chemoprevention. This review presents current knowledge as to the 5,6-EC metabolic pathway in BC focusing on the 5,6-EC metabolic enzymes ChEH and HSD11B2, and on 5,6-EC metabolite targets LXRβ and GR.
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https://www.hal.inserm.fr/inserm-03086999
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Submitted on : Wednesday, December 23, 2020 - 10:49:06 AM
Last modification on : Wednesday, February 24, 2021 - 11:22:03 AM

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Philippe de Médina, Khadijetou Diallo, Emilie Huc Claustre, Mehdi Attia, Régis Soulès, et al.. The 5,6-epoxycholesterol metabolic pathway in cancer: emergence of new pharmacological targets. British Journal of Pharmacology, Wiley, 2020, Online ahead of print. ⟨10.22541/au.159069407.75369904⟩. ⟨inserm-03086999⟩

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