Effect of chemopreventive agents on glutathione S-transferase P1-1 gene expression mechanisms via activating protein 1 and nuclear factor kappaB inhibition.
Biochem Pharmacol
; 68(6): 1101-11, 2004 Sep 15.
Article
in En
| MEDLINE
| ID: mdl-15313406
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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression
/
NF-kappa B
/
Apoptosis
/
Transcription Factor AP-1
/
Glutathione Transferase
/
Isoenzymes
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Biochem Pharmacol
Year:
2004
Document type:
Article
Affiliation country:
Luxembourg