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

Philippe de Médina 1, 2, 3 Michael R. Paillasse 1, 2, 3 Gregory Segala 1, 2, 4 Maud Voisin 1, 2, 4 Loubna Mhamdi 3 Florence Dalenc 1, 2, 4 Magali Lacroix-Triki 4 Thomas Filleron 4 Frederic Pont 5 Talal Al Saati 6 Christophe Morisseau 7 Bruce D. Hammock 7 Sandrine Silvente-Poirot 1, 2, 4 Marc Poirot 1, 2, 4 
IPBS - Institut de pharmacologie et de biologie structurale, CREFRE - Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales, GENOTOUL - Génopole Toulouse Midi-Pyrénées [Auzeville]
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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Submitted on : Monday, May 20, 2013 - 10:26:39 AM
Last modification on : Wednesday, June 1, 2022 - 4:27:13 AM

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Philippe de Médina, Michael R. 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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