Activation of peroxisome proliferator-activated receptor γ contributes to the survival of T lymphoma cells by affecting cellular metabolism

Chunyan Yang, Seung Hee Jo, B. Csernus, Elizabeth Hyjek, Yifang Liu, Amy Chadburn, Y. Lynn Wang

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ 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 PPARγ is expressed in human primary T-cell lymphoma tissues and activation of PPARγ with low doses of ligands protects lymphoma cells from serum starvation-induced apoptosis. The prosurvival effect of PPARγ was linked to its actions on cellular metabolic activities. In serum-deprived cells, PPARγ attenuated the decline in ATP, reduced mitochondrial hyperpolarization, and limited the amount of reactive oxygen species (ROS) in favor of cell survival. Moreover, PPARγ 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 PPARγ. These findings highlight the need for further investigation into the role of PPARγ in cancer before widespread use of its agonists as anticancer therapeutics.

Original languageEnglish
Pages (from-to)722-732
Number of pages11
JournalAmerican Journal of Pathology
Volume170
Issue number2
DOIs
Publication statusPublished - Feb 2007

Fingerprint

Peroxisome Proliferator-Activated Receptors
T-Cell Lymphoma
Survival
Ligands
Reactive Oxygen Species
Apoptosis
Cell Survival
Starvation
Serum
Antineoplastic Agents
Lymphoma
Neoplasms
Carcinogenesis
Homeostasis
Fatty Acids
Adenosine Triphosphate
Glucose

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Activation of peroxisome proliferator-activated receptor γ contributes to the survival of T lymphoma cells by affecting cellular metabolism. / Yang, Chunyan; Jo, Seung Hee; Csernus, B.; Hyjek, Elizabeth; Liu, Yifang; Chadburn, Amy; Wang, Y. Lynn.

In: American Journal of Pathology, Vol. 170, No. 2, 02.2007, p. 722-732.

Research output: Contribution to journalArticle

Yang, Chunyan ; Jo, Seung Hee ; Csernus, B. ; Hyjek, Elizabeth ; Liu, Yifang ; Chadburn, Amy ; Wang, Y. Lynn. / Activation of peroxisome proliferator-activated receptor γ contributes to the survival of T lymphoma cells by affecting cellular metabolism. In: American Journal of Pathology. 2007 ; Vol. 170, No. 2. pp. 722-732.
@article{be478b0ec14b40c2bbe450ec23fb09fa,
title = "Activation of peroxisome proliferator-activated receptor γ contributes to the survival of T lymphoma cells by affecting cellular metabolism",
abstract = "Peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ 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 PPARγ is expressed in human primary T-cell lymphoma tissues and activation of PPARγ with low doses of ligands protects lymphoma cells from serum starvation-induced apoptosis. The prosurvival effect of PPARγ was linked to its actions on cellular metabolic activities. In serum-deprived cells, PPARγ attenuated the decline in ATP, reduced mitochondrial hyperpolarization, and limited the amount of reactive oxygen species (ROS) in favor of cell survival. Moreover, PPARγ 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 PPARγ. These findings highlight the need for further investigation into the role of PPARγ in cancer before widespread use of its agonists as anticancer therapeutics.",
author = "Chunyan Yang and Jo, {Seung Hee} and B. Csernus and Elizabeth Hyjek and Yifang Liu and Amy Chadburn and Wang, {Y. Lynn}",
year = "2007",
month = "2",
doi = "10.2353/ajpath.2007.060651",
language = "English",
volume = "170",
pages = "722--732",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Activation of peroxisome proliferator-activated receptor γ contributes to the survival of T lymphoma cells by affecting cellular metabolism

AU - Yang, Chunyan

AU - Jo, Seung Hee

AU - Csernus, B.

AU - Hyjek, Elizabeth

AU - Liu, Yifang

AU - Chadburn, Amy

AU - Wang, Y. Lynn

PY - 2007/2

Y1 - 2007/2

N2 - Peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ 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 PPARγ is expressed in human primary T-cell lymphoma tissues and activation of PPARγ with low doses of ligands protects lymphoma cells from serum starvation-induced apoptosis. The prosurvival effect of PPARγ was linked to its actions on cellular metabolic activities. In serum-deprived cells, PPARγ attenuated the decline in ATP, reduced mitochondrial hyperpolarization, and limited the amount of reactive oxygen species (ROS) in favor of cell survival. Moreover, PPARγ 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 PPARγ. These findings highlight the need for further investigation into the role of PPARγ in cancer before widespread use of its agonists as anticancer therapeutics.

AB - Peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ 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 PPARγ is expressed in human primary T-cell lymphoma tissues and activation of PPARγ with low doses of ligands protects lymphoma cells from serum starvation-induced apoptosis. The prosurvival effect of PPARγ was linked to its actions on cellular metabolic activities. In serum-deprived cells, PPARγ attenuated the decline in ATP, reduced mitochondrial hyperpolarization, and limited the amount of reactive oxygen species (ROS) in favor of cell survival. Moreover, PPARγ 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 PPARγ. These findings highlight the need for further investigation into the role of PPARγ in cancer before widespread use of its agonists as anticancer therapeutics.

UR - http://www.scopus.com/inward/record.url?scp=33947501664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947501664&partnerID=8YFLogxK

U2 - 10.2353/ajpath.2007.060651

DO - 10.2353/ajpath.2007.060651

M3 - Article

VL - 170

SP - 722

EP - 732

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 2

ER -