Relationship between the methylation status of dietary flavonoids and their growth-inhibitory and apoptosis-inducing activities in human cancer cells.
Relationship between the methylation status of dietary flavonoids and their growth-inhibitory and apoptosis-inducing activities in human cancer cells.
复制标题
DOI：
10.1002/jcb.21853
复制
发表时间：
2008-10-01
影响因子：
4
通讯作者：
Dou, Q. Ping
中科院分区：
文献类型：
--
作者：
Landis-Piwowar, Kristin R.;Milacic, Vesna;Dou, Q. Ping
黄酮类化合物是广泛分布于植物界的多酚类化合物。令人信服的研究表明，黄酮类化合物在癌症化学预防和化学治疗中具有重要作用，这可能是由于生物活性，包括通过抗炎，自由基清除，调节生存/增殖途径和抑制泛素-蛋白酶体途径的作用。包括绿色茶多酚、（-）-表没食子儿茶素没食子酸酯或（-）-EGCG和类黄酮芹菜素、毛地黄黄酮、槲皮素和白杨素的植物多酚已经显示出抑制蛋白酶体活性并诱导人白血病细胞的凋亡。然而，生物转化反应的活性羟基的多酚会降低其生物活性。尽管甲基化多酚被认为在代谢上比未甲基化多酚更稳定，但甲基化多酚作为癌症预防剂的实际用途值得进一步研究。在本研究中，甲基化和未甲基化的黄酮类化合物的蛋白酶体抑制和诱导人白血病HL 60细胞凋亡的能力进行了研究。甲基化黄酮类化合物显示出持续的生物利用度，并通过将细胞阻滞在G1期来抑制细胞增殖。然而，它们在体外系统或计算机模型中均不作为蛋白酶体抑制剂，仅弱诱导细胞凋亡。与此相反，未甲基化的黄酮类化合物表现出抑制蛋白酶体活性在完整的HL 60细胞，积累蛋白酶体靶蛋白和诱导半胱天冬酶激活和聚（ADP-核糖）聚合酶裂解。我们的结论是，甲基化黄酮类化合物缺乏有效的细胞毒性对人类白血病细胞和最有可能有有限的能力作为化学预防剂。
Flavonoids are polyphenolic compounds widely distributed in the plant kingdom. Compelling research indicates that flavonoids have important roles in cancer chemoprevention and chemotherapy possibly due to biological activities that include action through anti-inflammation, free radical scavenging, modulation of survival/proliferation pathways, and inhibition of the ubiquitin-proteasome pathway. Plant polyphenols including the green tea polyphenol, (-)-epigallocatechin gallate or (-)-EGCG, and the flavonoids apigenin, luteolin, quercetin, and chrysin have been shown to inhibit proteasome activity and induce apoptosis in human leukemia cells. However, biotransformation reactions to the reactive hydroxyl groups on polyphenols could reduce their biological activities. Although methylated polyphenols have been suggested to be metabolically more stable than unmethylated polyphenols, the practical use of methylated polyphenols as a cancer preventative agent warrants further investigation. In the current study, methylated and unmethylated flavonoids were studied for their proteasome-inhibitory and apoptosis-inducing abilities in human leukemia HL60 cells. Methylated flavonoids displayed sustained bioavailability and inhibited cellular proliferation by arresting cells in the G1 phase. However, they did not act as proteasome inhibitors in either an in vitro system or an in silico model and only weakly induced apoptosis. In contrast, unmethylated flavonoids exhibited inhibition of the proteasomal activity in intact HL60 cells, accumulating proteasome target proteins and inducing caspase activation and poly (ADP-ribose) polymerase cleavage. We conclude that methylated flavonoids lack potent cytotoxicity against human leukemia cells and most likely have limited ability as chemopreventive agents.
登录
查看更多内容
影响因子：
6.7
作者：
Ban, Jung Ok;Hwang, In Gulk;Hong, Jin Tae
通讯作者：
Hong, Jin Tae
影响因子：
4.2
作者：
Choi, JS;Choi, YJ;Kang, YH
通讯作者：
Kang, YH
影响因子：
64.8
作者：
Groll, M;Ditzel, L;Huber, R
通讯作者：
Huber, R
影响因子：
5.6
作者：
Landis-Piwowar, Kristin R.;Wan, Sheng Biao;Dou, Q. Ping
通讯作者：
Dou, Q. Ping
影响因子：
12.4
作者：
An, B;Goldfarb, RH;Dou, QP
通讯作者：
Dou, QP