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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
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Sep 23, 2004
Volume
68
Issue
6
Pages
1111–1111
Identifiers
DOI: 10.1016/j.bcp.2004.05.032
Source
LBMCC
Keywords
License
Green

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 kappaB (NF-kappaB) are involved in its regulation. In the present study we examined the inhibitory effect of several chemopreventive agents on the tumor necrosis factor (TNF) alpha- 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 beta-lapachone, emodin, sanguinarine and capsaicin, which significantly inhibit reporter gene expression as well as TNFalpha- and TPA-induced binding of AP-1 and NF-kappaB, 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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