HX-1171, a Novel Nrf2 Activator, Induces NQO1 and HMOX1 Expression

J Cell Biochem. 2017 Oct;118(10):3372-3380. doi: 10.1002/jcb.25993. Epub 2017 May 3.

Abstract

HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone) is a novel synthesized vitamin E derivative, which reportedly has positive effects on various diseases and conditions, such as liver fibrosis, hepatic cirrhosis, and cancer. In this study, we analyzed the transcriptional activity induced by HX-1171. Results from reverse transcription polymerase chain reaction and promoter assays reveal that HX-1171 increased the expression of NQO1 and HMOX1, encoding antioxidant-related enzymes, in A549 human lung epithelial cells. The activity of nuclear factor-E2-related factor (Nrf2), a key transcriptional factor for antioxidative enzymes, was examined in HX-1171-treated cells. Confocal microscopy and Western blotting showed that HX-1171 effectively induced the nuclear translocation and transcriptional activity of Nrf2. We conclude that HX-1171, a novel Nrf2 activator, may be a promising therapeutic agent for oxidative stress-induced diseases. J. Cell. Biochem. 118: 3372-3380, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: ANTIOXIDANT; HX-1171; Nrf2; OXIDATIVE STRESS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Active Transport, Cell Nucleus / drug effects
  • Active Transport, Cell Nucleus / genetics
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Gene Expression Regulation / drug effects*
  • Heme Oxygenase-1 / biosynthesis*
  • Heme Oxygenase-1 / genetics
  • Humans
  • Hydroquinones / pharmacology*
  • NAD(P)H Dehydrogenase (Quinone) / biosynthesis*
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NF-E2-Related Factor 2 / antagonists & inhibitors*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics

Substances

  • Hydroquinones
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • 1-O-hexyl-2,3,5-trimethylhydroquinone
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human