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.