Research Papers:
NFκB/RelAPKM2 mediates inhibition of glycolysis by fenofibrate in glioblastoma cells
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Dongfeng Han1,*, Wenjin Wei1,*, Xincheng Chen1,*, Yaxuan Zhang1,*, Yingyi Wang1, Junxia Zhang1, Xiefeng Wang1, Tianfu Yu1, Qi Hu1, Ning Liu1, Yongping You1
1Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
*These authors have contributed equally to this work
Correspondence to:
Yongping You, e-mail: [email protected]
Keywords: fenofibrate, PPARα, RelA, PKM2, Warburg effect
Received: February 16, 2015 Accepted: June 19, 2015 Published: June 30, 2015
ABSTRACT
Aerobic glycolysis (production of lactate from glucose in the presence of oxygen) is a hallmark of cancer. Fenofibrate is a lipid-lowering drug and an agonist of the peroxisome proliferator-activated receptor alpha (PPARα). We found that FF inhibited glycolysis in a PPARα-dependent manner in glioblastoma cells. Fenofibrate inhibited the transcriptional activity of NF-κB/RelA and also disrupted its association with hypoxia inducible factor1 alpha (HIF1α), which is required for the binding of NF-κB/RelA to the PKM promoter and PKM2 expression. High ratios of PKM2/PKM1 promote glycolysis and inhibit oxidative phosphorylation, thus favoring aerobic glycolysis. Fenofibrate decreased the PKM2/PKM1 ratio and caused mitochondrial damage. Given that fenofibrate is a widely used non-toxic drug, we suggest its use in patients with glioblastoma multiforme (GBM).