title: Activation of peroxisome proliferator-activated receptor gamma contributes to the survival of T lymphoma cells by affecting cellular metabolism.
abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a metabolic regulator involved in maintaining glucose and fatty acid homeostasis. Besides its metabolic functions, the receptor has also been implicated in tumorigenesis. Ligands of PPARgamma induce apoptosis in several types of tumor cells, leading to the proposal that these ligands may be used as antineoplastic agents. However, apoptosis induction requires high doses of ligands, suggesting the effect may not be receptor-dependent. In this report, we show that PPARgamma is expressed in human primary T-cell lymphoma tissues and activation of PPARgamma with low doses of ligands protects lymphoma cells from serum starvation-induced apoptosis. The prosurvival effect of PPARgamma was linked to its actions on cellular metabolic activities. In serum-deprived cells, PPARgamma attenuated the decline in ATP, reduced mitochondrial hyperpolarization, and limited the amount of reactive oxygen species (ROS) in favor of cell survival. Moreover, PPARgamma regulated ROS through coordinated transcriptional control of a set of proteins and enzymes involved in ROS metabolism. Our study identified cell survival promotion as a novel activity of PPARgamma. These findings highlight the need for further investigation into the role of PPARgamma in cancer before widespread use of its agonists as anticancer therapeutics.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Yang
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Jo
authors.forename: Balazs
authors.initials: B
authors.lastname: Csernus
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hyjek
authors.forename: Yifang
authors.initials: Y
authors.lastname: Liu
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Y Lynn
authors.initials: YL
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008024:Ligands; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000819:agonists / Q000096:biosynthesis*; D047495:PPAR gamma / Q000819:agonists / Q000096:biosynthesis*; D020025:Peroxisome Proliferators / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: C477819:15-deoxyprostaglandin J2; D000970:Antineoplastic Agents; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D008024:Ligands; D009363:Neoplasm Proteins; D047495:PPAR gamma; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C006253:pirinixic acid; D000255:Adenosine Triphosphate; D005947:Glucose; D015230:Prostaglandin D2