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

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.

• Authors: Annelyse Duvoix, Sylvie Delhalle, Romain Blasius, Michaël Schnekenburger, Franck Morceau, Marjorie Fougère, Estelle Henry, Marie-Madeleine Galteau, Mario Dicato, Marc Diederich
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 68 Issue 6 Pg. 1101-11 (Sep 15 2004) ISSN: 0006-2952 [Print] England
• PMID: 15313406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Isoenzymes
• NF-kappa B
• Transcription Factor AP-1
• Tumor Necrosis Factor-alpha
• GSTP1 protein, human
• Glutathione S-Transferase pi
• Glutathione Transferase
• Tetradecanoylphorbol Acetate

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Chemoprevention
• Drug Interactions
• Gene Expression (drug effects)
• Glutathione S-Transferase pi
• Glutathione Transferase (genetics, metabolism)
• Humans
• Isoenzymes (genetics, metabolism)
• K562 Cells
• NF-kappa B (antagonists & inhibitors, metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)
• Transcription Factor AP-1 (antagonists & inhibitors, metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)
• U937 Cells