Induction of apoptosis by luteolin through cleavage of Bcl-2 family in human leukemia HL-60 cells

Eur J Pharmacol. 2005 Feb 10;509(1):1-10. doi: 10.1016/j.ejphar.2004.12.026. Epub 2005 Jan 21.


In our study, luteolin has shown its apoptosis-inducing potent in HL-60 cells with its 76.5% apoptotic ratio of 100 microM treatment. When HL-60 cells were treated with 60 microM of luteolin, DNA ladders were visible at 6 h and increased from 6-12 h after treatment. Luteolin could decrease the mitochondrial membrane potential, trigger cytochrome c released to cytosol, and subsequently induce the processing of procaspase-9 and procaspase-3, which were followed by the cleavage of poly-(ADP-ribose) polymerase (PARP) and DNA fragmentation factor (DFF-45). The cleavage of the proapoptotic Bcl-2 proteins, such as Bad and Bax to produce their truncated forms, and the cleavage of the antiapoptotic Bcl-2 proteins, such as Bcl-2 and Bcl-XL, into their potent pro-apoptotic fragments were detected in our study. From the results, we suggested that the structure of luteolin contributes to its potent in inducing apoptosis in HL-60 cells, and the mitochondrial pathway might play an important role in the luteolin-induced apoptosis. The induction of apoptosis by luteolin may offer a pivotal mechanism for its cancertherapeutic and chemopreventive action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Caspase 3
  • Caspase 9
  • Caspases / drug effects
  • Caspases / metabolism
  • Cytochromes c / drug effects
  • Cytochromes c / metabolism
  • DNA Fragmentation / drug effects*
  • DNA Fragmentation / physiology
  • Dose-Response Relationship, Drug
  • Flavones / adverse effects*
  • Flavones / chemistry
  • Flavones / metabolism
  • HL-60 Cells*
  • Humans
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Models, Biological
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / adverse effects*
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Time Factors


  • Flavones
  • Proto-Oncogene Proteins c-bcl-2
  • Cytochromes c
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
  • Caspases