Effect of citrus flavonoids on HL-60 cell differentiation

Twenty-seven Citrus flavonoids were examined for their activity of inductio n of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific e sterase, and phagocytic activities. 10 flavonoids were judged to be active (percentage of NBT reducing cells was more than 40 % at a concentration of 40 mu M), and the rank order of potency was natsudaidain, luteolin, tangere tin, quercetin, apigenin, 3, 3, '4, '5, 6, 7, 8-heptamethoxyflavone, nobile tin, acacetin, eriodictyol, and taxifolin. These flavonoids exerted their a ctivity in a dose-dependent manner. HL-60 cells treated with these flavonoi ds differentiated into mature monocyte/macrophage. The structure-activity r elationship established from comparison between flavones and flavanones rev ealed that ortho-catechol moiety in ring B and C2-C3 double bond had an imp ortant role for induction of differentiation of HL-60. In polymethoxylated flavones, hydroxyl group at C3 and methoxyl group at C8 enhanced the differ entiation-inducing activity.