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Effect of chemopreventive agents on glutathione S-transferase P1-1 gene expression mechanisms via activating protein 1 and nuclear factor kappaB inhibition

Authors
  • Duvoix, Annelyse
  • Delhalle, Sylvie
  • Blasius, Romain
  • Schnekenburger, Michaël
  • Morceau, Franck
  • Fougère, Marjorie
  • Henry, Estelle
  • Galteau, Marie-Madeleine
  • Dicato, Mario
  • Diederich, Marc
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Jan 01, 2004
Accepted Date
May 18, 2004
Volume
68
Issue
6
Pages
1101–1111
Identifiers
DOI: 10.1016/j.bcp.2004.05.032
Source
Elsevier
Keywords
License
Unknown

Abstract

Glutathione S-transferase P1-1 (GSTP1-1) is a phase II drug metabolism enzyme implicated in carcinogenesis and development of resistance to anti-cancer drugs. It was previously shown that both activating protein 1 (AP-1) and nuclear factor κB (NF-κB) are involved in its regulation. In the present study we examined the inhibitory effect of several chemopreventive agents on the tumor necrosis factor (TNF) α- or 12-O-tetradecanoylphorbol 13 acetate (TPA)-induced promoter activity of GSTP1-1, as demonstrated by transient transfection experiments in K562 and U937 leukemia cells. Our results provide evidence for a differential effect of chemopreventive agents such as β-lapachone, emodin, sanguinarine and capsaicin, which significantly inhibit reporter gene expression as well as TNFα- and TPA-induced binding of AP-1 and NF-κB, whereas trans-anethole and silymarin do not produce any inhibitory effect. Our results demonstrate the ability of selected chemopreventive agents to decrease GSTP1-1 gene expression mechanisms and could thus contribute to reduce the incidence of glutathione related drug resistance in human leukemia.

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