[Effects of flavonoids with different structures on proliferation of leukemia cell line HL-60].
OBJECTIVE
Flavonoids, with some beneficial biological activities, exist extensively in foods and herbal products. This study was to evaluate the effects of 23 flavonoids on the proliferation of leukemia cell line HL-60, and elucidate the structure-activity relationship (SAR).


METHODS
HL-60 cells were treated with 23 flavonoids with high purity and definite structure. Cell proliferation was detected by MTT assay. The 50% inhibition concentrations (IC50) of the 23 flavonoids were calculated. The effects of particular structures on IC50 were evaluated.


RESULTS
Most of the 23 flavonoids inhibited the proliferation of HL-60 cells distinctly, and the effects were enhanced along with increasing concentrations. However, the intensity of their effects were different, which were arranged from strong to weak as follows:3,6-dihydroxyflavone > luteolin > geraldol > 2'-hydroxyflavanone > apigenin > 3,7-dihydroxyflavone > myricetin > fisetin > baicalein > quercetin > flavanone > chrysin > galangin > 4'-hydroxyflavanone > 6-hydroxyflavone > genistein > flavone >7-hydroxyflavone > daidzein > hesperetin > naringenin. The 2,3-double bond in ring C, appropriate hydroxyls, ring B attached at position 2, hydroxyls in position 3, ortho-substituting hydroxyls in ring B were related to enhanced inhibitory effects of flavonoids on the proliferation of HL-60 cells, while the lack of 2,3-double bond, deficiency or redundancy of hydroxyl groups, hydroxyl group in position 5, 7 or meta-substituting hydroxyls in ring B, isoflavone structure were related to reduced inhibitory effects of flavonoids.


CONCLUSIONS
The 2,3-double bond in ring C, appropriate hydroxyls, ring B attached at position 2, hydroxyls in position 3, ortho-substituting hydroxyls in ring B may be key structural requirements of flavonoids for potent cytotoxicity to HL-60 cells.
Chang
Hui
H
Department of Nutrition and Food Hygiene, College of Preventive Medicine, Third Military University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, 400038, PR China.
Mi
Man-Tian
MT
Gu
Yan-Yan
YY
Yuan
Jia-Lin
JL
Ling
Wen-Hua
WH
Lin
Hui
H
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D047311:Luteolin / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D047310:Apigenin; D047311:Luteolin; C422925:3,7-dihydroxyflavone