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, Marc Poirot

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62 Scopus citations

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.

Original languageEnglish (US)
Article number1840
JournalNature Communications
Volume4
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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    De Medina, P., Paillasse, M. R., Segala, G., Voisin, M., Mhamdi, L., Dalenc, F., Lacroix-Triki, M., Filleron, T., Pont, F., Saati, T. A., Morisseau, C., Hammock, B. D., Silvente-Poirot, S., & Poirot, M. (2013). Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties. Nature Communications, 4, [1840]. https://doi.org/10.1038/ncomms2835