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Nat Commun. 2013;4:1840. doi: 10.1038/ncomms2835.

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

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1
INSERM UMR 1037, Team Sterol Metabolism and Therapeutic Innovations in Oncology, Cancer Research Center of Toulouse, F-31052 Toulouse, France.

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.

PMID:
23673625
PMCID:
PMC3674249
DOI:
10.1038/ncomms2835
[Indexed for MEDLINE]
Free PMC Article
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