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Titre du document / Document title

Fatty acid metabolism in breast cancer cells : differential inhibitory effects of epigallocatechin gallate (EGCG) and C75

Auteur(s) / Author(s)

PUIG Teresa (1 2) ; VAZQUEZ-MARTIN Alejandro (1 3) ; RELAT Joana (4) ; PETRIZ Jordi (5) ; MENENDEZ Javier A. (1 3) ; PORTA Rut (1 3) ; CASALS Gemma (1) ; MARRERO Pedro F. (4) ; HARO Diego (4) ; BRUNET Joan (3) ; COLOMER Ramon (3 6) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Fundació d'Investigació Biomèdica de Girona Dr. Josep Trueta (IdIBGi), Hospital Universitari de Girona Dr. Josep Trueta, Girona, ESPAGNE
(2) Biochemistry and Molecular Biology, School of Sciences, University of Girona, Girona, ESPAGNE
(3) Medical Oncology, Institut Català d'Oncologia de Girona (ICO Girona), Hospital Universitari de Girona Dr. Josep Trueta, Avda. França s/n, 17007 Girona, ESPAGNE
(4) Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Barcelona, ESPAGNE
(5) Biomedical Research Unit, Hospital Vall d'Hebron, Barcelona, ESPAGNE
(6) MD Anderson Cancer Center España, Madrid, ESPAGNE

Résumé / Abstract

Endogenous fatty acid metabolism is crucial to maintain the cancer cell malignant phenotype. Lipogenesis is regulated by the enzyme fatty acid synthase (FASN); and breakdown of fatty acids is regulated by camitine palmitoyltransferase-1 (CPT-I). FASN is highly expressed in breast cancer and most common human carcinomas. Several compounds can inhibit FASN, although the degree of specificity of this inhibition has not been addressed. We have tested the effects of C75 and (-)-epigallocatechin-3-gallate (EGCG) on fatty acid metabolism pathways, cellular proliferation, induction of apoptosis and cell signalling in human breast cancer cells. Our results show that C75 and EGCG had comparable effects in blocking FASN activity. Treating cancer cells with EGCG or C75 induced apoptosis and caused a decrease in the active forms of oncoprotein HER2, AKT and ERK1/2 to a similar degree. We observed, in contrast, marked differential effects between C75 and EGCG on the fatty acid oxidation pathway. While EGCG had either no effect or a moderate reduction in CPT-I activity, C75 stimulated CPT-I activity (up to 129%), even in presence of inhibitory levels of malonyl-CoA, a potent inhibitor of the CPT-I enzyme. Taken together, these findings indicate that pharmacological inhibition of FASN occurs uncoupled from the stimulation of CPT-I with EGCG but not with C75, suggesting that EGCG might be free of the CPT-I related in vivo weight-loss that has been associated with C75. Our results establish EGCG as a potent and specific inhibitor of fatty acid synthesis (FASN), which may hold promise as a target-directed anti-cancer drug.

Revue / Journal Title

Breast cancer research and treatment    ISSN  0167-6806   CODEN BCTRD6 

Source / Source

2008, vol. 109, no3, pp. 471-479 [9 page(s) (article)] (31 ref.)

Langue / Language

Anglais

Editeur / Publisher

Springer, Dordrecht, PAYS-BAS  (1981) (Revue)

Mots-clés anglais / English Keywords

Phenols

;

Breast disease

;

Mammary gland diseases

;

Cancer

;

Malignant tumor

;

Pharmacokinetics

;

Lipids

;

Epigallocatechin gallate

;

Inhibitor

;

Drug

;

Antineoplastic agent

;

Flavonoid

;

Polyphenol

;

Tumor cell

;

Breast cancer

;

Metabolism

;

Fatty acids

;

Mots-clés français / French Keywords

Phénols

;

Pathologie du sein

;

Pathologie de la glande mammaire

;

Cancer

;

Tumeur maligne

;

Pharmacocinétique

;

Lipide

;

Epigallocatéchine gallate

;

Inhibiteur

;

Médicament

;

Anticancéreux

;

Flavonoïde

;

Polyphénol

;

Cellule tumorale

;

Cancer du sein

;

Métabolisme

;

Acide gras

;

Mots-clés espagnols / Spanish Keywords

Fenoles

;

Seno patología

;

Glándula mamaria patología

;

Cáncer

;

Tumor maligno

;

Farmacocinética

;

Lípido

;

Inhibidor

;

Medicamento

;

Anticanceroso

;

Flavonoide

;

Polifenol

;

Célula tumoral

;

Cáncer del pecho

;

Metabolismo

;

Acido graso

;

Mots-clés d'auteur / Author Keywords

Anti-cancer drug

;

Breast cancer

;

C75

;

EGCG

;

Fatty acid inhibitors

;

Fatty acid metabolism

;

Localisation / Location

INIST-CNRS, Cote INIST : 20699, 35400018319179.0070

Nº notice refdoc (ud4) : 20370121



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