Effect of citrus flavonoids on HL-60 cell differentiation.
Twenty-seven Citrus flavonoids were examined for their activity of induction of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific esterase, and phagocytic activities. 10 flavonoids were judged to be active (percentage of NBT reducing cells was more than 40% at a concentration of 40 microM), and the rank order of potency was natsudaidain, luteolin, tangeretin, quercetin, apigenin, 3, 3, '4, '5, 6, 7, 8-heptamethoxyflavone, nobiletin, acacetin, eriodictyol, and taxifolin. These flavonoids exerted their activity in a dose-dependent manner. HL-60 cells treated with these flavonoids differentiated into mature monocyte/macrophage. The structure-activity relationship established from comparison between flavones and flavanones revealed that ortho-catechol moiety in ring B and C2-C3 double bond had an important role for induction of differentiation of HL-60. In polymethoxylated flavones, hydroxyl group at C3 and methoxyl group at C8 enhanced the differentiation-inducing activity.
Kawaii
S
S
National Institute of Fruit Tree Science, Shizuoka, Japan.
Tomono
Y
Y
Katase
E
E
Ogawa
K
K
Yano
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002957:Citrus; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects*; D006801:Humans; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005419:Flavonoids; D009580:Nitroblue Tetrazolium