Induction of apoptosis by curcumin: mediation by glutathione S-transferase P1-1 inhibition.

Abstract

Expression of glutathione S-transferase P1-1 (GSTP1-1) is correlated to carcinogenesis and resistance of cancer cells against chemotherapeutic agents. Curcumin, a natural compound extracted from Curcuma longa, has shown strong antioxidant and anticancer properties and also the ability to regulate a wide variety of genes that require activating protein 1 and nuclear factor kappaB (NF-kappaB) activation. In the present study, we examined the inhibitory effect of curcumin on the expression of GSTP1-1 mRNA as well as protein, and we correlated this inhibition with the apoptotic effect of curcumin on K562 leukemia cells. Curcumin efficiently inhibited the tumour necrosis factor alpha- and phorbol ester-induced binding of AP-1 and NF-kappaB transcription factors to sites located on the GSTP1-1 gene promoter. TNFalpha-induced GSTP1-1 promoter activity was also inhibited by curcumin as shown by reporter gene assay. In parallel, curcumin induced pro-caspases 8 and 9 as well as poly ADP ribose polymerase cleavage and thus leading to apoptosis in K562 cells. Our results overall add a novel role for curcumin as this chemoprotective compound could contribute to induce apoptosis by its ability to inhibit the GSTP1-1 expression at the level of transcription.

• Authors: Annelyse Duvoix, Franck Morceau, Sylvie Delhalle, Martine Schmitz, Michaël Schnekenburger, Marie-Madeleine Galteau, Mario Dicato, Marc Diederich
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 66 Issue 8 Pg. 1475-83 (Oct 15 2003) ISSN: 0006-2952 [Print] England
• PMID: 14555224 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Isoenzymes
• NF-kappa B
• RNA, Messenger
• Transcription Factor AP-1
• Tumor Necrosis Factor-alpha
• GSTP1 protein, human
• Glutathione S-Transferase pi
• Glutathione Transferase
• Curcumin
• Tetradecanoylphorbol Acetate

Topics

• Apoptosis
• Cell Survival (drug effects)
• Curcumin (pharmacology)
• Drug Interactions
• Enzyme Inhibitors (pharmacology)
• Glutathione S-Transferase pi
• Glutathione Transferase (antagonists & inhibitors)
• Humans
• Isoenzymes (antagonists & inhibitors)
• K562 Cells
• NF-kappa B (metabolism)
• RNA, Messenger (biosynthesis, drug effects)
• Tetradecanoylphorbol Acetate (pharmacology)
• Transcription Factor AP-1 (metabolism)
• Transcription, Genetic (drug effects)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, pharmacology)