ROS accumulation and IGF-IR inhibition contribute to fenofibrate/PPARα -mediated inhibition of Glioma cell motility in vitro

Molecular Cancer

Research

Justyna Drukala¹  Ewa Wybieralska¹  Zbigniew Madeja¹  Maja Grabacka²  Katarzyna Urbanska³  Anna Wilk⁴  Luis Del Valle⁴  Krzysztof Reiss⁴ 

[1] Department of Cell Biology, Faculty of Biotechnology, Jagiellonian University, Krakow, Poland;Department of Food Biotechnology, Faculty of Food Technology, Agricultural University of Krakow, Krakow, Poland;Department of Genetics, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA;Neurological Cancer Research, Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA;

关键词: Glioma Cell;    Fenofibrate;    Glioma Cell Line;    Reactive Oxygen Species Accumulation;    T98G Cell;   

DOI  :  10.1186/1476-4598-9-159

 received in 2009-12-08, accepted in 2010-06-22,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundGlioblastomas are characterized by rapid cell growth, aggressive CNS infiltration, and are resistant to all known anticancer regimens. Recent studies indicate that fibrates and statins possess anticancer potential. Fenofibrate is a potent agonist of peroxisome proliferator activated receptor alpha (PPARα) that can switch energy metabolism from glycolysis to fatty acid β-oxidation, and has low systemic toxicity. Fenofibrate also attenuates IGF-I-mediated cellular responses, which could be relevant in the process of glioblastoma cell dispersal.MethodsThe effects of fenofibrate on Glioma cell motility, IGF-I receptor (IGF-IR) signaling, PPARα activity, reactive oxygen species (ROS) metabolism, mitochondrial potential, and ATP production were analyzed in human glioma cell lines.ResultsFenofibrate treatment attenuated IGF-I signaling responses and repressed cell motility of LN-229 and T98G Glioma cell lines. In the absence of fenofibrate, specific inhibition of the IGF-IR had only modest effects on Glioma cell motility. Further experiments revealed that PPARα-dependent accumulation of ROS is a strong contributing factor in Glioma cell lines responses to fenofibrate. The ROS scavenger, N-acetyl-cysteine (NAC), restored cell motility, improved mitochondrial potential, and increased ATP levels in fenofibrate treated Glioma cell lines.ConclusionsOur results indicate that although fenofibrate-mediated inhibition of the IGF-IR may not be sufficient in counteracting Glioma cell dispersal, PPARα-dependent metabolic switch and the resulting ROS accumulation strongly contribute to the inhibition of these devastating brain tumor cells.

【 授权许可】

Unknown   
© Drukala et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.