Antineoplastic Agents; Receptors, Cytoplasmic and Nuclear; Transcription Factors; Animals; Antineoplastic Agents/pharmacology; Antineoplastic Agents/therapeutic use; Apoptosis/drug effects; Cell Line, Tumor; Clinical Trials as Topic; Humans; Models, Animal; Neoplasms/drug therapy; Receptors, Cytoplasmic and Nuclear/agonists; Receptors, Cytoplasmic and Nuclear/therapeutic use; Signal Transduction/physiology; Transcription Factors/agonists; Transcription Factors/pharmacology; Transcription Factors/therapeutic use; Oncology
Abstract :
[en] Peroxisome proliferator-activated receptors (PPAR) are members of a superfamily of nuclear hormone receptors. Activation of PPAR isoforms elicits both antineoplastic and anti-inflammatory effects in several types of mammalian cells. PPARs are ligand-activated transcription factors and have a subfamily of three different isoforms: PPAR alpha, PPAR gamma, and PPAR beta/delta. All isoforms heterodimerise with the 9-cis-retinoic acid receptor RXR, and play an important part in the regulation of several metabolic pathways, including lipid biosynthesis and glucose metabolism. Endogenous ligands of PPAR gamma include long-chain polyunsaturated fatty acids, eicosanoid derivates, and oxidised lipids. Newly developed synthetic ligands include thiazolidinediones-a group of potent PPAR gamma agonists and antidiabetic agents. Here, we review PPAR gamma-induced antineoplastic signalling pathways, and summarise the antineoplastic effects of PPAR gamma agonists in different cancer cell lines, animal models, and clinical trials.
Disciplines :
Neurology
Author, co-author :
Grommes, Christian; Department of Neurosciences, Alzheimer Research Laboratory, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
Landreth, Gary E; Department of Neurosciences, Alzheimer Research Laboratory, Case Western Reserve University, Cleveland, OH, United States
HENEKA, Michael ; Department of Neurology, University of Bonn Medical Center, D-53127 Bonn, Germany
External co-authors :
yes
Language :
English
Title :
Antineoplastic effects of peroxisome proliferator-activated receptor gamma agonists.
GEL has received financial support for research projects on antiinflammatory actions of PPARγ agonists by GlaxoSmithKline.CG is supported by a grant from the Deutsche Forschungsgemeinschaft (GR 2018/1-1).
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