Elimination of nq01 gene expression by vitamin e

Jill M. Kolesar, Robert L. Talbert, John G. Kuhn

Research output: Contribution to journalReview article

Abstract

Objective. NQ01 codes for NAD(P)H:Quinone ox idoreductase (NQOR, DT-diaphorase) which cata lyzes the two electron reduction of quinones. NQOR may protect against quinone-mediated carci nogenicity and activate bioreductive alkylating agents. NQ01 gene expression is induced in response to variety of stimuli, including oxidative stress. Gene expression of NQ01 in response to the antioxidant vitamin E was investigated in this case report. Case Summary. Baseline NQ01 gene expression was 7.5 X 10-6 ng NQ01/mL cDNA in one healthy, male (age 46) adult nonsmoking volunteer. The subject subsequently began taking vitamin E (α-tocoph erol, Bronson) 400 IU/d. NQ01 gene expression after 30 days of vitamin E administration was undetectable. The volunteer discontinued vitamin E and NQ01 gene expression was 1.46 X 10-6 ng NQ01/mL cDNA after 30 days. Vitamin E was restarted and after 30 and 60 days, NQ01 gene expression was again undetectable. Discussion: In this subject we have demonstrated the ability of vitamin E to effectively eliminate NQ01 gene expression in vivo as measured by a quantitative RT-PCR CE-LIF assay. Vitamin E modulates signal transduction pathways in response to oxidative stress possibly by downregulation of nuclear factor kappa B (NF-kB). NF-B, in turn, increases the gene transcription of NQ01. We hypothesize that vitamin E decreases the gene expression of NQ01 by this signaling pathway; by decreasing NF-KB, which in turn downregulates NQ01 gene expression. This may be important for oncology patients because as demonstrated in vitro, decreased NQOR activity results in resistance to mitomycin-C. Conclusion. Treatment with pharmacological doses of vitamin E can result in NQ01 gene expression down regulation in vivo when analyzed by RT-PCR CE-LIF. This interaction, role in the signaling. cascade, and its potential influence on an individuals response to chemotherapy represents an important avenue of exploration.

Original languageEnglish (US)
Pages (from-to)121-123
Number of pages3
JournalJournal of Oncology Pharmacy Practice
Volume2
Issue number2
DOIs
Publication statusPublished - Dec 1 1996

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Keywords

  • CE-LIF
  • DT-diaphorase
  • NQ01
  • Quantitative RT-PCR
  • Vitamin E

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

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