Role of the p50 subunit of NF-κB in vitamin E-induced changes in mice treated with the peroxisome proliferator, ciprofibrate

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15 Scopus citations


Peroxisome proliferators (PPs) are a diverse class of chemicals, which cause a dramatic increase in the size and number of hepatic peroxisomes in rodents and eventually lead to the development of hepatic tumors. Nuclear factor-κB (NF-κB) is a transcription factor activated by reactive oxygen and is involved in cell proliferation and apoptosis. Previously we found that the peroxisome proliferator ciprofibrate (CIP) activates NF-κB and that dietary vitamin E decreases CIP-induced NF-κB DNA binding. We, therefore, hypothesized that inhibition of NF-κB by vitamin E is necessary for effects of vitamin E on CIP-induced cell proliferation and the inhibition of apoptosis by CIP. Sixteen B6129 female mice (p50+/+) and twenty mice deficient in the p50 subunit of NF-κB (p50-/-) were fed a purified diet containing 10 or 250 mg/kg vitamin E (α-tocopherol acetate) for 28 days. At that time, half of the mice were placed on the same diet with 0.01% CIP for 10 days. CIP treatment increased the DNA binding activity of NF-κB and cell proliferation, but had no significant effect on apoptosis. Compared to wild-type mice, the p50-/- mice had lower NF-κB activation, higher basal levels of cell proliferation and apoptosis, and a lower ratio of reduced glutathione to oxidized glutathione (GSH/GSSG). There was approximately a 60% reduction in cell proliferation in the CIP-treated p50-/- mice fed higher vitamin E in comparison to the p50-/- mice fed lower vitamin E. Dietary vitamin E also inhibited the DNA binding activity of NF-κB, increased apoptosis, and increased the GSH/GSSG ratio. This study shows the effects of vitamin E on cell growth parameters do not appear to be solely through decreased NF-κB activation, suggesting that vitamin E is acting by other molecular mechanisms.

Original languageEnglish
Pages (from-to)2062-2073
Number of pages12
JournalFood and Chemical Toxicology
Issue number6
StatePublished - Jun 2008

Bibliographical note

Funding Information:
The authors thank Job Tharappel, Zijing Lu, and Michelle Twaroski for their assistance with the animal study. In addition, we thank Larry Robertson for the use of his HPLC. This work was supported by National Institutes of Health Grant ES-11480 and by the Kentucky Agricultural Experimental Station. K.C.M. was supported by a National Institutes of Health training Grant (CA-09509).


  • Cell proliferation
  • Ciprofibrate
  • NF-κB
  • Vitamin E

ASJC Scopus subject areas

  • Food Science
  • Toxicology


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