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Measurement of Heme Synthesis Levels in Mammalian Cells
09:43

Measurement of Heme Synthesis Levels in Mammalian Cells

Published on: July 9, 2015

Structural influence of isothiocyanates on the antioxidant response element (ARE)-mediated heme oxygenase-1 (HO-1)

Auemduan Prawan1, Young-Sam Keum, Tin Oo Khor

  • 1Department of Pharmacology, Faculty of Medicine, Khon Kaen University, 123 Mittrapharb Road, Khon Kaen, 40002, Thailand.

Pharmaceutical Research
|July 28, 2007
PubMed
Abstract

Insights

Isothiocyanates (ITCs) activate the Nrf2/ARE pathway to induce heme oxygenase-1 (HO-1), a key antioxidant enzyme. Their cancer chemopreventive effects are structure-dependent, with potential for synthetic ITCs to outperform natural ones.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Isothiocyanates (ITCs) from cruciferous vegetables are potent chemopreventive agents.
  • ITCs modulate phase II detoxifying/antioxidant enzymes, but their structure-activity relationship (SAR) is underexplored.
  • Heme oxygenase-1 (HO-1) is a crucial antioxidant enzyme induced by ITCs.

Purpose of the Study:

  • To investigate the SAR of ITCs on antioxidant response element (ARE)-mediated HO-1 induction.
  • To evaluate the role of Nrf2 in ITC-induced HO-1 expression.
  • To explore the potential of synthetic ITCs as chemopreventive agents.

Main Methods:

  • Human hepatoma HepG2-C8 cells were treated with ten ITCs.
  • Assays included cell viability, luciferase reporter assay, Western blot, and quantitative real-time PCR.
  • Nrf2 knockout (Nrf2-/-) mouse embryonic fibroblasts and Nrf2 dominant-negative mutant (Nrf2-M4) were used.

Main Results:

  • Most ITCs significantly induced ARE-mediated luciferase activity and HO-1 protein expression.
  • HO-1 induction correlated with Nrf2 protein levels.
  • ITC-induced HO-1 expression was dependent on Nrf2 and linked to glutathione depletion.

Conclusions:

  • ITCs activate ARE-mediated HO-1 transcription via the Nrf2/ARE pathway.
  • ITC-induced effects are structure-specific, suggesting synthetic ITCs may offer enhanced chemoprevention.
  • This study elucidates the molecular mechanisms underlying ITC chemopreventive activity.

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