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

Philippe de Medina, Michael R. Paillasse, Gregory Segala, Maud Voisin, Loubna Mhamdi, Florence Dalenc, Magali Lacroix-Triki, Thomas Filleron, Frederic Pont, Talal Al Saati, Christophe Morisseau, Bruce D. Hammock, Sandrine Silvente-Poirot () and Marc Poirot ()
Additional contact information
Philippe de Medina: INSERM UMR 1037, Team ‘Sterol Metabolism and Therapeutic Innovations in Oncology’, Cancer Research Center of Toulouse
Michael R. Paillasse: INSERM UMR 1037, Team ‘Sterol Metabolism and Therapeutic Innovations in Oncology’, Cancer Research Center of Toulouse
Gregory Segala: INSERM UMR 1037, Team ‘Sterol Metabolism and Therapeutic Innovations in Oncology’, Cancer Research Center of Toulouse
Maud Voisin: INSERM UMR 1037, Team ‘Sterol Metabolism and Therapeutic Innovations in Oncology’, Cancer Research Center of Toulouse
Loubna Mhamdi: AFFICHEM
Florence Dalenc: INSERM UMR 1037, Team ‘Sterol Metabolism and Therapeutic Innovations in Oncology’, Cancer Research Center of Toulouse
Magali Lacroix-Triki: University Toulouse III
Thomas Filleron: Institut Claudius Regaud
Frederic Pont: UDEAR, UMR 5165 CNRS-University Toulouse III
Talal Al Saati: INSERM-US006 ANEXPLO/CREFRE
Christophe Morisseau: University of California
Bruce D. Hammock: University of California
Sandrine Silvente-Poirot: INSERM UMR 1037, Team ‘Sterol Metabolism and Therapeutic Innovations in Oncology’, Cancer Research Center of Toulouse
Marc Poirot: INSERM UMR 1037, Team ‘Sterol Metabolism and Therapeutic Innovations in Oncology’, Cancer Research Center of Toulouse

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms2835

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