Flavones and polyphenols inhibit the NO pathway during apoptosis of leukemia B-cells.
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.
Quiney
Claire
C
INSERM E 355, Centre Biomédical des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
Dauzonne
Daniel
D
Kern
Catherine
C
Fourneron
Jean-Dominique
JD
Izard
Jean-Claude
JC
Mohammad
Ramzi M
RM
Kolb
Jean-Pierre
JP
Billard
Christian
C
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology*; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015448:Leukemia, B-Cell / Q000378:metabolism / Q000473:pathology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D019253:Proto-Oncogene Proteins c-bcl-2; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D019253:Proto-Oncogene Proteins c-bcl-2; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases