title: PPARα Antagonist AA452 Triggers Metabolic Reprogramming and Increases Sensitivity to Radiation Therapy in Human Glioblastoma Primary Cells.
abstract: Glioblastoma (GB) is the most common cancer in the brain and with an increasing incidence. Despite major advances in the field, there is no curative therapy for GB to date. Many solid tumors, including GB, experienced metabolic reprogramming in order to sustain uncontrolled proliferation, hypoxic conditions, and angiogenesis. PPARs, member of the steroid hormone receptor superfamily, are particularly involved in the control of energetic metabolism, particularly lipid metabolism, which has been reported deregulated in gliomas. PPARα was previously indicated by us as a potential therapeutic target for this neoplasm, due to the malignancy grade dependency of its expression, being particularly abundant in GB. In this work, we used a new PPARα antagonist on patient-derived GB primary cells, with particular focus on the effects on lipid metabolism and response to radiotherapy. The results obtained demonstrated that blocking PPARα results in cell death induction, increase of radiosensitivity, and decrease of migration. Therefore, AA452 is proposed as a new adjuvant for the gold standard therapies for GB, opening the possibility for preclinical and clinical trials for this class of compounds. J. Cell. Physiol. 232: 1458-1466, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Depatment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Benedetti
authors.affiliation: Depatment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: d'Angelo
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ammazzalorso
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Gravina
authors.affiliation: Institute of Endocrinology and Experimental Oncology (IEOS), CNR, Naples, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Laezza
authors.affiliation: Depatment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antonosante
authors.affiliation: Depatment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Panella
authors.affiliation: Depatment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Cinque
authors.affiliation: Depatment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Cristiano
authors.affiliation: Depatment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Anne Chloè
authors.initials: AC
authors.lastname: Dhez
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, Pennsylvania.|Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Astarita
authors.affiliation: Depatment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Galzio
authors.affiliation: Depatment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cifone
authors.affiliation: Depatment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Ippoliti
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Amoroso
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Di Cesare
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, Pennsylvania.|Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Depatment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.|Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, Pennsylvania.|Gran Sasso National Laboratory (LNGS), National Institute for Nuclear Physics (INFN), Assergi, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cimini
mesh_terms: D000328:Adult; D000368:Aged; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D002465:Cell Movement; D020869:Gene Expression Profiling; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D013194:Staining and Labeling; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: C000618762:AA452 compound; D052160:Benzothiazoles; D014408:Biomarkers, Tumor; D005904:Glial Fibrillary Acidic Protein; D047493:PPAR alpha; D013449:Sulfonamides