Studies on the inhibitory effects of quercetin on the growth of HL-60 leukemia cells.
Quercetin, a naturally occurring flavonoid, has been shown to exert multiple pharmacological effects and to be an anticancer agent or a supplementary anticancer agent. In this report, the human HL-60 promyelocytic leukemia cell line was used to study the effects of quercetin on the growth, cell cycle, activities of cytosolic and membrane protein kinase C (PKC) and tyrosine protein kinase (TPK), and phosphoinositide production of the tumor cells. The results showed that quercetin inhibited the growth of HL-60 cells in a concentration-dependent manner, with an IC50 value of about 7.7 microM after 96 hr of treatment; when the concentration of quercetin was 10 microM, the percent inhibition on the growth of HL-60 cells was 17.1, 27.3, 40.1, and 52.7% after 24, 48, 72, and 96 hr of treatment, respectively. Flow cytometric analyses showed that quercetin caused an increase in cells in the G2/M phase and a decrease in cells in the G0/G1 phase of the cell cycle in a concentration-dependent manner; these effects were reversed when quercetin was removed from the culture medium. Quercetin strongly inhibited the activities of cytosolic PKC and membrane TPK from HL-60 cells in vitro, with IC50 values of about 30.9 and 20.1 microM, respectively, but did not affect membrane PKC or cytosolic TPK activity from HL-60 cells in vitro. Quercetin markedly inhibited in a concentration-dependent manner the production of phosphoinositides in intact HL-60 cells. The results provide evidence that the inhibitory effect of quercetin on the growth of HL-60 cells may be related to its inhibitory effects on PKC and/or TPK in vitro and/or on the production of phosphoinositides.
Kang
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TB
Institute of Medical Biochemistry, Guangdong Medical College, Zhanjiang, P.R. China. zjlys@pub.zhangjiang.gd.cn
Liang
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NC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010716:Phosphatidylinositols; D011794:Quercetin; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C