Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties. - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2013

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

(1, 2, 3) , (1, 2, 3) , (1, 2, 4) , (1, 2, 4) , (3) , (1, 2, 4) , (4) , (4) , (5) , (6) , (7) , (7) , (1, 2, 4) , (1, 2, 4)
1
2
3
4
5
6
7
Loubna Mhamdi
  • Function : Author
Thomas Filleron
Talal Al Saati
  • Function : Author

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.

Dates and versions

inserm-00823974 , version 1 (20-05-2013)

Identifiers

Cite

Philippe de Médina, Michael R. Paillasse, Gregory Segala, Maud Voisin, Loubna Mhamdi, et al.. Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties.. Nature Communications, 2013, 4, pp.1840. ⟨10.1038/ncomms2835⟩. ⟨inserm-00823974⟩
248 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More