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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Body Fluids / metabolism
  • Brain / metabolism
  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Cholestanols / chemistry
  • Cholestanols / pharmacology*
  • Cholestanols / therapeutic use
  • Cholesterol / metabolism*
  • Epoxide Hydrolases / antagonists & inhibitors
  • Epoxide Hydrolases / metabolism
  • Female
  • Histamine / metabolism*
  • Humans
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Imidazoles / therapeutic use
  • Immunocompetence / drug effects
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Lymphocytes / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Receptors, Estrogen / metabolism
  • Survival Analysis
  • Tissue Extracts


  • 5-hydroxy-6-(2-(1H-imidazol-4-yl)ethylamino)cholestan-3-ol
  • Antineoplastic Agents
  • Cholestanols
  • Imidazoles
  • Receptors, Estrogen
  • Tissue Extracts
  • Histamine
  • Cholesterol
  • Epoxide Hydrolases
  • cholesterol-5 alpha,6 alpha-epoxide hydrase