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NF-?B/RelA-PKM2 mediates inhibition of glycolysis by fenofibrate in glioblastoma cells.

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 (PPAR?). We found that FF inhibited glycolysis in a PPAR?-dependent manner in glioblastoma cells. Fenofibrate inhibited the transcriptional activity of NF-?B/RelA and also disrupted its association with hypoxia inducible factor1 alpha (HIF1?), which is required for the binding of NF-?B/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).

SUBMITTER: Han D

PROVIDER: S-EPMC4694890 | biostudies-other | 2015 Sep

REPOSITORIES: biostudies-other

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NF-κB/RelA-PKM2 mediates inhibition of glycolysis by fenofibrate in glioblastoma cells.

Han Dongfeng D Wei Wenjin W Chen Xincheng X Zhang Yaxuan Y Wang Yingyi Y Zhang Junxia J Wang Xiefeng X Yu Tianfu T Hu Qi Q Liu Ning N You Yongping Y

Oncotarget 20150901 28

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-κ ...[more]

PMID: 26172294

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