title: When cholesterol meets histamine, it gives rise to dendrogenin A: a tumour suppressor metabolite.
abstract: Dendrogenin A (DDA) is the first steroidal alkaloid (SA) to be identified in human tissues to date and arises from the stereoselective enzymatic conjugation of 5,6α-epoxycholesterol (5,6α-EC) with histamine (HA). DDA induces the re-differentiation of cancer cellsin vitroandin vivoand prevents breast cancer (BC) and melanoma development in mice, evidencing its protective role against oncogenesis. In addition, DDA production is lower in BCs compared with normal tissues, suggesting a deregulation of its biosynthesis during carcinogenesis. The discovery of DDA reveals the existence of a new metabolic pathway in mammals which lies at the crossroads of cholesterol and HA metabolism and which leads to the production of this metabolic tumour suppressor.
authors.affiliation: Sterol Metabolism and Therapeutic Innovations, Cancer Research Center of Toulouse, INSERM UMR 1037, University of Toulouse, F-31037 Toulouse, France Institut Claudius Regaud, Institut Universitaire du Cancer, F-31059 Toulouse, France marc.poirot@inserm.fr sandrine.poirot@inserm.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Poirot
authors.affiliation: Sterol Metabolism and Therapeutic Innovations, Cancer Research Center of Toulouse, INSERM UMR 1037, University of Toulouse, F-31037 Toulouse, France Institut Claudius Regaud, Institut Universitaire du Cancer, F-31059 Toulouse, France marc.poirot@inserm.fr sandrine.poirot@inserm.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Silvente-Poirot
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002777:Cholestanols / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D051379:Mice
chemical_list: C582666:5-hydroxy-6-(2-(1H-imidazol-4-yl)ethylamino)cholestan-3-ol; D016588:Anticarcinogenic Agents; D002777:Cholestanols; D007093:Imidazoles; D006632:Histamine; D002784:Cholesterol
keywords: 6-epoxide hydrolase; cancer; cholesterol; cholesterol-5; dendrogenin; steroidal alkaloid; tamoxifen