Flavonoid effects on normal and leukemic cells☆

Abstract 

Quercetin and flavopiridol, both flavonoids which influence oxidative milieu, proliferation, and apoptosis of various cell types, were examined for their effects on acute myelogenous leukemic cells and normal progenitors. Both quercetin and flavopiridol inhibited the growth and viability of various acute myelogenous leukemia (AML) cell lines and AML blasts isolated afresh from patients with AML of various subtypes. The effects on inhibition of proliferation and decreased viability were also significant in normal CD34+ cells isolated from normal marrow donors. In certain AML cases, the effects of flavopiridol appeared to be mediated through activation of caspase 3, offering one possible mechanism for the apoptosis evident after exposure to flavopiridol as measured by annexin V expression. These flavonoid compounds might find use in various therapeutic settings in AML.

Abbreviations:  AML, acute myelogenous leukemia, PBS, phosphate buffered saline, EDTA, ethylenediamine tetraacetic acid, BSA, bovine serum albumin, FcR, Fc receptor, FACS, fluorescence activated cell sorting, LTC-IC, long-term culture initiating cell, CFU-GM, granulocyte–macrophage colony forming unit, AML-CFC, AML colony forming cell, TdT, terminal deoxynucleotidyl transferase, PI, propidium iodide, GM-CSF, granulocyte–macrophage colony stimulating factor, IL-3, interleukin-3, SCF, stem cell factor, FAB, French American British

Keywords:  Quercetin, Flavopiridol, Apoptosis, Proliferation, Caspase 3