Kang T B, Liang N C
Institute of Medical Biochemistry, Guangdong Medical College, Zhanjiang, P.R. China.
Biochem Pharmacol. 1997 Nov 1;54(9):1013-8. doi: 10.1016/s0006-2952(97)00260-8.
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.
槲皮素是一种天然存在的黄酮类化合物，已被证明具有多种药理作用，是一种抗癌剂或辅助抗癌剂。在本报告中，使用人HL-60早幼粒细胞白血病细胞系来研究槲皮素对肿瘤细胞生长、细胞周期、胞质和膜蛋白激酶C（PKC）及酪氨酸蛋白激酶（TPK）活性以及磷酸肌醇生成的影响。结果表明，槲皮素以浓度依赖的方式抑制HL-60细胞的生长，处理96小时后IC50值约为7.7微摩尔；当槲皮素浓度为10微摩尔时，处理24、48、72和96小时后对HL-60细胞生长的抑制率分别为17.1%、27.3%、40.1%和52.7%。流式细胞术分析表明，槲皮素以浓度依赖的方式使细胞周期中G2/M期的细胞增加，G0/G1期的细胞减少；当从培养基中去除槲皮素时，这些作用会逆转。槲皮素在体外强烈抑制HL-60细胞的胞质PKC和膜TPK活性，IC50值分别约为30.9和20.1微摩尔，但不影响HL-60细胞体外膜PKC或胞质TPK活性。槲皮素以浓度依赖的方式显著抑制完整HL-60细胞中磷酸肌醇的生成。结果提供了证据表明，槲皮素对HL-60细胞生长的抑制作用可能与其在体外对PKC和/或TPK以及/或者对磷酸肌醇生成的抑制作用有关。
