5,7,3′-trihydroxy-3,4′-dimethoxyflavone-induced cell death in human leukemia cells is dependent on caspases and activates the MAPK pathway

Fernando Torres, José Quintana, Francisco Estévez

Research output: Contribution to journalArticlepeer-review


Flavonoids are polyphenolic compounds which display a vast array of biological activities and are promising anticancer agents. In this study we investigated the effect of 5,7,3′-trihydroxy-3,4′-dimethoxyflavone (THDF) on viability of nine human tumor cell lines and found that it was highly cytotoxic against leukemia cells. THDF induced G 2-M phase cell-cycle arrest and apoptosis through a caspase-dependent mechanism involving cytochrome c release, processing of multiple caspases (caspase-3, -6, -7, and -9) and cleavage of poly(ADP-ribose) polymerase. Overexpression of the protective mitochondrial proteins Bcl-2 and Bcl-x L conferred partial resistance to THDF-induced apoptosis. This flavonoid induced the phosphorylation of members of the mitogen-activated protein kinases (MAPKs) family and cell death was attenuated by inhibition of c-jun N-terminal kinases/stress-activated protein kinases (JNK/SAPK) and of extracellular signal-regulated kinases (ERK) 1/2. In the present study we report that THDF-induced cell death is mediated by an intrinsic dependent apoptotic event involving mitochondria and MAPKs, and through a mechanism independent of the generation of reactive oxygen species. The results suggest that THDF could be useful in the development of novel anticancer agents.

Original languageEnglish
Pages (from-to)464-475
Number of pages12
JournalMolecular Carcinogenesis
Issue number5
Publication statusPublished - May 2010


  • Apoptosis
  • c-jun N-terminal kinases
  • Cell-cycle arrest
  • Extracellular signal-regulated kinases
  • Flavonoids
  • Mitogen-activated protein kinases

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology


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