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

Annelyse Duvoix, Franck Morceau, Sylvie Delhalle, Martine Schmitz, Michaël Schnekenburger, Marie Madeleine Galteau, Mario Dicato, Marc Diederich*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

125 Citations (Scopus)

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 languageEnglish
Pages (from-to)1475-1483
Number of pages9
JournalBiochemical Pharmacology
Volume66
Issue number8
DOIs
Publication statusPublished - 15 Oct 2003
Externally publishedYes

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

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