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Transcriptional regulation of glutathione S-transferase P1-1 in human leukemia

Authors
Type
Published Article
Journal
BioFactors
Publisher
Wiley (John Wiley & Sons)
Publication Date
Aug 23, 2003
Volume
17
Issue
1-4
Pages
138–138
Identifiers
DOI: 10.1002/biof.5520170113
Source
LBMCC
Keywords
License
Yellow

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 kB (NF-kB) 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 a- and phorbol ester-induced binding of AP-1 and NF-kB transcription factors to sites located on the GSTP1-1 gene promoter. TNFa-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.

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