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

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 ε-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.

Abbreviations:  NO, nitric oxide, iNOS, inducible NO synthase, RTA, resveratrol triacetate, VFPA, ε-viniferin pentaacetate, B-CLL, B-cell chronic lymphocytic leukemia, ALL, acute lymphoblastic leukemia, HCL, hairy cell leukemia, PS, phosphatidyl serine, PI, propidium iodide, DAF-2 DA, diaminofluorescein 2-diacetate, HRP, horseradish peroxidase, IAP, inhibitor of apoptosis proteins

Keywords:  Apoptosis, NO, iNOS, Leukemia B-cells, Flavones, Polyphenols