Bryonolic Acid Blocks Cancer Cell Clonogenicity and Invasiveness through the Inhibition of Fatty Acid: Cholesteryl Ester Formation.

Biomedicines. 2018 Feb 12;6(1). pii: E21. doi: 10.3390/biomedicines6010021. Free full text http://www.mdpi.com/2227-9059/6/1/21 Khallouki F1,2,3, Owen RW4, Silvente-Poirot S5, Poirot M6. Author information 1 Division of Preventive Oncology, National Center for Tumor Diseases, Im Neuenheimer Feld 460 and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg 69120, Germany. farid_khallouki@yahoo.fr. 2 Team of Endocrinology and Nutrition Physiology, Faculté des Sciences et Techniques d'Errachidia (FSTE), Université Moulay Ismail, 509, Boutalamine, Errachidia 52000, Morocco. farid_khallouki@yahoo.fr. 3 Cancer Research Center of Toulouse, Unité Mixte de Recherche (UMR) 1037 Institut National de la Santé et de la Recherche Médicale (INSERM)-University of Toulouse III, Toulouse F-31037, France. farid_khallouki@yahoo.fr. 4 Division of Preventive Oncology, National Center for Tumor Diseases, Im Neuenheimer Feld 460 and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg 69120, Germany. Robert.Owen@nct-heidelberg.de. 5 Cancer Research Center of Toulouse, Unité Mixte de Recherche (UMR) 1037 Institut National de la Santé et de la Recherche Médicale (INSERM)-University of Toulouse III, Toulouse F-31037, France. sandrine.poirot@inserm.fr. 6 Cancer Research Center of Toulouse, Unité Mixte de Recherche (UMR) 1037 Institut National de la Santé et de la Recherche Médicale (INSERM)-University of Toulouse III, Toulouse F-31037, France. marc.poirot@inserm.fr. Abstract Bryonolic acid (BrA) is a pentacyclic triterpene present in several plants used in African traditional medicine such as Anisophyllea dichostyla R. Br. Here we investigated the in vitro anticancer properties of BrA. We report that BrA inhibits acyl-coA: cholesterol acyl transferase (ACAT) activity in rat liver microsomes in a concentration-dependent manner, blocking the biosynthesis of the cholesterol fatty acid ester tumour promoter. We next demonstrated that BrA inhibits ACAT in intact cancer cells with an IC50 of 12.6 ± 2.4 µM. BrA inhibited both clonogenicity and invasiveness of several cancer cell lines, establishing that BrA displays specific anticancer properties. BrA appears to be more potent than the other pentacyclic triterpenes, betulinic acid and ursolic acid studied under similar conditions. The inhibitory effect of BrA was reversed by exogenous addition of cholesteryl oleate, showing that ACAT inhibition is responsible for the anticancer effect of BrA. This report reveals new anticancer properties for BrA. KEYWORDS: ChEH; cancer cell; cholesterol; cholesteryl esters; colony formation; invasiveness; metabolism; tumour promoter PMID: 29439506 DOI: 10.3390/biomedicines6010021 Free full text