Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes

Yoshimasa Nakamura, Chiho Yoshida, Akira Murakami, Hajime Ohigashi, Toshihiko Osawa, Koji Uchida

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Zerumbone (ZER), a sesquiterpene compound occurring in tropical ginger Zingiber zerumbet Smith, has been implicated as one of the promising chemopreventive agents against colon and skin cancer. In the present study, we investigated the phase II detoxification enzymes induction of ZER using a cultured rat normal liver epithelial cell line. Exposure of RL34 cells to ZER resulted in the significant induction of glutathione S-transferase, while the reduced analogues of ZER (α-humulene and 8-hydroxy-α-humulene) did not show any inducing effect. Therefore, the electrophilic property, characterized by the reactivity with intracellular nucleophiles including protein sulfhydryls as well as low molecular weight thiols, at the 8-position α,β-unsaturated carbonyl group plays an important role in the induction of phase II enzymes. ZER induced nuclear localization of the transcription factor Nrf2 that binds to antioxidant response element (ARE) of the phase II enzyme genes, suggesting that ZER is a potential activator of the Nrf2/ARE-dependent detoxification pathway. This is consistent with the observation that ZER potentiated the gene expression of several Nrf2/ARE-dependent phase II enzyme genes, including γ-glutamylcysteine synthetase, glutathione peroxidase, and hemeoxygenase-1. The present study also implied the antioxidant role of this detoxification system activation by ZER in the neutralization of lipid peroxidation in hepatocytes, providing a new insight for cancer prevention.

Original languageEnglish
Pages (from-to)245-250
Number of pages6
JournalFEBS Letters
Volume572
Issue number1-3
DOIs
Publication statusPublished - Aug 13 2004
Externally publishedYes

Fingerprint

Ginger
Sesquiterpenes
Antioxidant Response Elements
Enzymes
Pharmaceutical Preparations
Detoxification
Phase II Metabolic Detoxication
Genes
Glutamate-Cysteine Ligase
Nucleophiles
Enzyme Induction
Heme Oxygenase-1
zerumbone
Skin Neoplasms
Glutathione Transferase
Sulfhydryl Compounds
Gene expression
Liver
Colonic Neoplasms
Lipid Peroxidation

Keywords

  • α,β-unsaturated carbonyl
  • Antioxidant
  • Cancer prevention
  • Detoxification
  • Electrophile
  • Glutathione
  • Glutathione S-transferase
  • RL34
  • Zerumbone

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes. / Nakamura, Yoshimasa; Yoshida, Chiho; Murakami, Akira; Ohigashi, Hajime; Osawa, Toshihiko; Uchida, Koji.

In: FEBS Letters, Vol. 572, No. 1-3, 13.08.2004, p. 245-250.

Research output: Contribution to journalArticle

Nakamura, Y, Yoshida, C, Murakami, A, Ohigashi, H, Osawa, T & Uchida, K 2004, 'Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes', FEBS Letters, vol. 572, no. 1-3, pp. 245-250. https://doi.org/10.1016/j.febslet.2004.07.042
Nakamura, Yoshimasa ; Yoshida, Chiho ; Murakami, Akira ; Ohigashi, Hajime ; Osawa, Toshihiko ; Uchida, Koji. / Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes. In: FEBS Letters. 2004 ; Vol. 572, No. 1-3. pp. 245-250.
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