Metabolism and anticancer activity of the curcumin analogue, dimethoxycurcumin
Metabolism and anticancer activity of the curcumin analogue, dimethoxycurcumin
复制标题
DOI：
10.1158/1078-0432.ccr-06-1839
复制
发表时间：
2007-02-15
影响因子：
11.5
通讯作者：
Pantazis, Panayotis
中科院分区：
文献类型：
--
作者：
Tamvakopoulos, Constantin;Dimas, Konstantinos;Pantazis, Panayotis
目的：植物源化合物姜黄素在体外和体内显示出作为癌症化学预防和化学治疗剂的有前途的能力，但表现出较差的生物利用度。因此，有必要研究改进的抗癌活性和药代动力学property.Experimental设计：合成的姜黄素类似物二甲氧基姜黄素与姜黄素的能力进行了比较，以抑制增殖和凋亡的人HCT 116结肠癌细胞在体外通过估计GI（50）和LC 50值和检测细胞周期的流式细胞术分析的凋亡程度。在体外与小鼠和人肝微粒体和癌细胞孵育后，通过最近开发的质谱方法评价代谢物的代谢稳定性和/或鉴别。此外，循环中的二甲氧基姜黄素和姜黄素的水平测定小鼠腹腔注射administration.Results：二甲氧基姜黄素是显着更有效的比姜黄素在抑制HCT 116细胞的增殖和诱导凋亡处理48小时。几乎100%的姜黄素，
Purpose: The plant-derived compound curcumin has shown promising abilities as a cancer chemoprevention and chemotherapy agent in vitro and in vivo but exhibits poor bioavailability. Therefore, there is a need to investigate modified curcumin congeners for improved anticancer activity and pharmacokinetic properties.Experimental Design: The synthetic curcumin analogue dimethoxycurcumin was compared with curcumin for ability to inhibit proliferation and apoptosis of human HCT116 colon cancer cells in vitro by estimating the GI(50) and LC50 values and detecting the extent of apoptosis by flow cytometry analysis of the cell cycle. Metabolic stability and/or identification of metabolites were evaluated by recently developed mass spectrometric approaches after incubation with mouse and human liver microsomes and cancer cells in vitro. Additionally, circulating levels of dimethoxycurcumin and curcumin were determined in mice following i.p. administration.Results: Dimethoxycurcumin is significantly more potent than curcumin in inhibiting proliferation and inducing apoptosis in HCT116 cells treated for 48 h. Nearly 100% of curcumin but