title: [6]-Gingerol inhibits de novo fatty acid synthesis and carnitine palmitoyltransferase-1 activity which triggers apoptosis in HepG2.
abstract: The de novo fatty acid synthesis catalyzed by key lipogenic enzymes, including fatty acid synthase (FASN) has emerged as one of the novel targets of anti-cancer approaches. The present study explored the possible inhibitory efficacy of [6]-gingerol on de novo fatty acid synthesis associated with mitochondrial-dependent apoptotic induction in HepG2 cells. We observed a dissipation of mitochondrial membrane potential accompanied by a reduction of fatty acid levels. [6]-gingerol administration manifested inhibition of FASN expression, indicating FASN is a major target of [6]-gingerol inducing apoptosis in HepG2 cells. Indeed, we found that increased ROS generation could likely be a mediator of the anti-cancer effect of [6]-gingerol. A reduction of fatty acid levels and induction of apoptosis were restored by inhibition of acetyl-CoA carboxylase (ACC) activity, suggesting an accumulation of malonyl-CoA level could be the major cause of apoptotic induction of [6]-gingerol in HepG2 cells. The present study also showed that depletion of fatty acid following [6]-gingerol treatment caused an inhibitory effect on carnitine palmitoyltransferase-1 activity (CPT-1), whereas C75 augmented CPT-1 activity, indicating that [6]-gingerol exhibits the therapeutic benefit on suppression of fatty acid β-oxidation.
authors.affiliation: Department of Physiology, Faculty of Medical Science, Naresuan University Phitsanulok, Thailand 65000.
authors.forename: Hathaichanok
authors.initials: H
authors.lastname: Impheng
authors.affiliation: Laboratoire de Toxicologie Cellulaire, Faculté de Médecine et de Pharmacie, Université de Franche-Comté Besançon, France.
authors.forename: Lysiane
authors.initials: L
authors.lastname: Richert
authors.affiliation: Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University Phitsanulok, Thailand 6500.
authors.forename: Dumrongsak
authors.initials: D
authors.lastname: Pekthong
authors.affiliation: Faculty of Pharmaceutical Sciences, Naresuan University Phitsanulok, Thailand 65000.
authors.forename: C Norman
authors.initials: CN
authors.lastname: Scholfield
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Naresuan University Phitsanulok, Thailand 65000 ; Centre of Excellence in Medical Biotechnology (CEMB), Faculty of Medical Science, Naresuan University Phitsanulok, Thailand 65000.
authors.forename: Sutatip
authors.initials: S
authors.lastname: Pongcharoen
authors.affiliation: Department of Anatomy, Faculty of Medical Science, Naresuan University Phitsanulok, Thailand 65000.
authors.forename: Ittipon
authors.initials: I
authors.lastname: Pungpetchara
authors.affiliation: Department of Physiology, Faculty of Medical Science, Naresuan University Phitsanulok, Thailand 65000.
authors.forename: Piyarat
authors.initials: P
authors.lastname: Srisawang
keywords: Carnitine palmitoyltransferase-1 (CPT-1)/de novo fatty acid synthesis/fatty acid synthase (FASN)/[6]-gingerol/malonyl-CoA