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

• Published in: Biochemical pharmacology 2004-09, Vol.68 (6), p.1101-1111
• Main Authors: Duvoix, Annelyse, Delhalle, Sylvie, Blasius, Romain, Schnekenburger, Michaël, Morceau, Franck, Fougère, Marjorie, Henry, Estelle, Galteau, Marie-Madeleine, Dicato, Mario, Diederich, Marc
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Biological and medical sciences; Carcinogenesis; Chemoprevention; Chemopreventive agents; Drug Interactions; Drug resistance; Gene Expression - drug effects; Glutathione S-Transferase pi; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; GSTP1-1; Humans; Isoenzymes - genetics; Isoenzymes - metabolism; K562 Cells; Leukemia; Medical sciences; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Pharmacology. Drug treatments; Tetradecanoylphorbol Acetate - pharmacology; Transcription Factor AP-1 - antagonists & inhibitors; Transcription Factor AP-1 - metabolism; Tumor Necrosis Factor-alpha - pharmacology; U937 Cells
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2004.05.032

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.