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

Research output: Contribution to journalArticle

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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

Fingerprint

histamines
cholesterol
metabolism
Metabolism
Histamine
Tumors
Cell Differentiation
mammals
tumors
Cholesterol
cells
Neoplasms
alkaloids
epoxy compounds
metabolites
Mammals
conjugation
cultured cells
breast
integrity

ASJC Scopus subject areas

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

Cite this

De Medina, P., Paillasse, M. R., Segala, G., Voisin, M., Mhamdi, L., Dalenc, F., ... 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

Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties. / De Medina, Philippe; Paillasse, Michael R.; Segala, Gregory; Voisin, Maud; Mhamdi, Loubna; Dalenc, Florence; Lacroix-Triki, Magali; Filleron, Thomas; Pont, Frederic; Saati, Talal Al; Morisseau, Christophe; Hammock, Bruce D.; Silvente-Poirot, Sandrine; Poirot, Marc.

In: Nature Communications, Vol. 4, 1840, 2013.

Research output: Contribution to journalArticle

De Medina, P, Paillasse, MR, Segala, G, Voisin, M, Mhamdi, L, Dalenc, F, Lacroix-Triki, M, Filleron, T, Pont, F, Saati, TA, Morisseau, C, Hammock, BD, Silvente-Poirot, S & Poirot, M 2013, 'Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties', Nature Communications, vol. 4, 1840. https://doi.org/10.1038/ncomms2835
De Medina, Philippe ; Paillasse, Michael R. ; Segala, Gregory ; Voisin, Maud ; Mhamdi, Loubna ; Dalenc, Florence ; Lacroix-Triki, Magali ; Filleron, Thomas ; Pont, Frederic ; Saati, Talal Al ; Morisseau, Christophe ; Hammock, Bruce D. ; Silvente-Poirot, Sandrine ; Poirot, Marc. / Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties. In: Nature Communications. 2013 ; Vol. 4.
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