Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties.

Abstract : We previously synthesized dendrogenin A and hypothesized that it could be a natural metabolite occurring in mammals. Here we explore this hypothesis and report the discovery of dendrogenin A in mammalian tissues and normal cells as an enzymatic product of the conjugation of 5,6α-epoxy-cholesterol and histamine. Dendrogenin A was not detected in cancer cell lines and was fivefold lower in human breast tumours compared with normal tissues, suggesting a deregulation of dendrogenin A metabolism during carcinogenesis. We established that dendrogenin A is a selective inhibitor of cholesterol epoxide hydrolase and it triggered tumour re-differentiation and growth control in mice and improved animal survival. The properties of dendrogenin A and its decreased level in tumours suggest a physiological function in maintaining cell integrity and differentiation. The discovery of dendrogenin A reveals a new metabolic pathway at the crossroads of cholesterol and histamine metabolism and the existence of steroidal alkaloids in mammals.
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Nature Communications, Nature Publishing Group, 2013, 4, pp.1840. 〈10.1038/ncomms2835〉
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Contributeur : Marc Poirot <>
Soumis le : lundi 20 mai 2013 - 10:26:39
Dernière modification le : jeudi 11 janvier 2018 - 06:23:24

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Philippe De Medina, Michael Paillasse, Gregory Segala, Maud Voisin, Loubna Mhamdi, et al.. Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties.. Nature Communications, Nature Publishing Group, 2013, 4, pp.1840. 〈10.1038/ncomms2835〉. 〈inserm-00823974〉

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