title: Fenofibrate Induces Ketone Body Production in Melanoma and Glioblastoma Cells.
abstract: Ketone bodies [beta-hydroxybutyrate (bHB) and acetoacetate] are mainly produced in the liver during prolonged fasting or starvation. bHB is a very efficient energy substrate for sustaining ATP production in peripheral tissues; importantly, its consumption is preferred over glucose. However, the majority of malignant cells, particularly cancer cells of neuroectodermal origin such as glioblastoma, are not able to use ketone bodies as a source of energy. Here, we report a novel observation that fenofibrate, a synthetic peroxisome proliferator-activated receptor alpha (PPARa) agonist, induces bHB production in melanoma and glioblastoma cells, as well as in neurospheres composed of non-transformed cells. Unexpectedly, this effect is not dependent on PPARa activity or its expression level. The fenofibrate-induced ketogenesis is accompanied by growth arrest and downregulation of transketolase, but the NADP/NADPH and GSH/GSSG ratios remain unaffected. Our results reveal a new, intriguing aspect of cancer cell biology and highlight the benefits of fenofibrate as a supplement to both canonical and dietary (ketogenic) therapeutic approaches against glioblastoma.
authors: Department of Food Biotechnology, Faculty of Food Technology, University of Agriculture , Krakow , Poland.
authors: Maja M
authors: MM
authors: Grabacka
authors: Molecular and Metabolic Oncology Program, Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama , Mobile, AL , USA.
authors: Anna
authors: A
authors: Wilk
authors: Department of Food Biotechnology, Faculty of Food Technology, University of Agriculture , Krakow , Poland.
authors: Anna
authors: A
authors: Antonczyk
authors: Department of Human Nutrition, Faculty of Food Technology, University of Agriculture , Krakow , Poland.
authors: Paula
authors: P
authors: Banks
authors: Department of Food Biotechnology, Faculty of Food Technology, University of Agriculture , Krakow , Poland.
authors: Emilia
authors: E
authors: Walczyk-Tytko
authors: Neurological Cancer Research, Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center , New Orleans, LA , USA.
authors: Matthew
authors: M
authors: Dean
authors: Department of Food Biotechnology, Faculty of Food Technology, University of Agriculture , Krakow , Poland.
authors: Malgorzata
authors: M
authors: Pierzchalska
authors: Neurological Cancer Research, Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center , New Orleans, LA , USA.
authors: Krzysztof
authors: K
authors: Reiss
keywords: 3-hydroxy-3-methylglutaryl-CoA synthetase 2; beta-hydroxybutyrate; peroxisome proliferator-activated receptor alpha; transketolase