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 κB (NF-κB) 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 α- and phorbol ester-induced binding of AP-1 and NF-κB transcription factors to sites located on the GSTP1-1 gene promoter. TNFα-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.
Original language | English |
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Pages (from-to) | 1475-1483 |
Number of pages | 9 |
Journal | Biochemical Pharmacology |
Volume | 66 |
Issue number | 8 |
DOIs | |
Publication status | Published - 15 Oct 2003 |
Externally published | Yes |
Keywords
- 12-O-tetradecanoylphorbol-13-acetate
- AP-1
- Activating protein 1
- Apoptosis
- Carcinogenesis
- Curcumin
- Drug resistance
- GST
- GSTP1-1
- Glutathione S-transferase
- Leukemia
- NF-κB
- Nuclear factor κB
- TNFα
- TPA
- Tumour necrosis factor α