Flavones and polyphenols inhibit the NO pathway during apoptosis of leukemia B-cells

Leuk Res. 2004 Aug;28(8):851-61. doi: 10.1016/j.leukres.2003.12.003.

Abstract

We recently reported that resveratrol, a grape-derived polyphenol, in vitro induces the apoptosis of leukemic B-cells and simultaneously inhibits the production of endogenous nitric oxide (NO) through inducible NO synthase (iNOS) down-regulation. The same results were observed in the present study with not only acetate derivatives of polyphenols, particularly the pentaacetate of -viniferin (resveratrol dimer), but also with a synthetic flavone (a diaminomethoxyflavone) in both leukemia B-cell lines and B-cell chronic lymphocytic leukemia (B-CLL) patients' cells. Moreover, flavopiridol, another flavone already known for its pro-apoptotic properties in B-CLL cells, was also found to down-regulate both iNOS expression and NO production. Thus, inhibition of the NO pathway during apoptosis of leukemia B-cells appears a common mechanism for several compounds belonging to two distinct families of phytoalexins, the flavones and grape-derived polyphenols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / metabolism
  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / metabolism
  • Cell Division / drug effects
  • Down-Regulation
  • Flavonoids / pharmacology*
  • Gene Expression Regulation, Leukemic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Leukemia, B-Cell / metabolism
  • Leukemia, B-Cell / pathology*
  • Membrane Potentials / drug effects
  • Mitochondria
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Phenols / pharmacology*
  • Polyphenols
  • Proto-Oncogene Proteins c-bcl-2
  • Signal Transduction / drug effects*
  • Tumor Cells, Cultured

Substances

  • Annexin A5
  • Flavonoids
  • Phenols
  • Polyphenols
  • Proto-Oncogene Proteins c-bcl-2
  • Nitric Oxide
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • CASP3 protein, human
  • Caspase 3
  • Caspases