Inhibition of cell proliferation by a resveratrol analog in human pancreatic and breast cancer cells
Inhibition of cell proliferation by a resveratrol analog in human pancreatic and breast cancer cells
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DOI：
10.3858/emm.2009.41.3.018
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发表时间：
2009-03-31
影响因子：
12.8
通讯作者：
Bae, Insoo
中科院分区：
文献类型：
--
作者：
Bin Hong, Young;Kang, Hyo Jin;Bae, Insoo
据报道，白藜芦醇具有预防癌症的特性。在这项研究中，我们分析了新合成的白藜芦醇类似物cia 3，4 '，5-三甲氧基-3'-羟基二苯乙烯（以下称为11b）对乳腺癌和胰腺癌细胞系的抗肿瘤活性。11b处理降低了人胰腺癌和乳腺癌细胞的增殖，将细胞阻滞在G2/M期，并增加了亚G1/G 0级分中的细胞百分比。11 B处理还增加了有丝分裂检查点蛋白如BubR 1、Aurora B、细胞周期蛋白B和磷酸化组蛋白H3的总水平。从机制上讲，11b在体外阻断微管聚合，并扰乱了胰腺癌和乳腺癌细胞系中的微管网络。11b-微管蛋白相互作用的计算建模表明，11b的二甲氧基苯基可以结合到微管蛋白的秋水仙素结合位点。我们的研究表明，11b的治疗效果发生在较低的浓度比与白藜芦醇治疗相关的类似效果，微管可能是观察到的11b的效果的主要目标。这些研究表明，11b应进一步检查作为一个潜在的有效的临床化疗药物治疗胰腺癌和乳腺癌患者。
Resveratrol has been reported to possess cancer preventive properties. In this study, we analyzed anti-tumor activity of a newly synthesized resveratrol analog, cia3,4',5-trimethoxy-3'-hydroxystilbene (hereafter called 11b) towards breast and pancreatic cancer cell lines. 11b treatments reduced the proliferation of human pancreatic and breast cancer cells, arrested cells in the G2/M phase, and increased the percentage of cells in the subG1/G0 fraction. The 11b treatments also increased the total levels of mitotic checkpoint proteins such as BubR1, Aurora B, Cyclin B, and phosphorylated histone H3. Mechanistically, 11b blocks microtubule polymerization in vitro and it disturbed microtubule networks in both pancreatic and breast cancer cell lines. Computational modeling of the 11b-tubulin interaction indicates that the dimethoxyphenyl group of 11b can bind to the colchicine binding site of tubulin. Our studies show that the 11b treatment effects occur at lower concentrations than similar effects associated with resveratrol treatments and that microtubules may be the primary target for the observed effects of 11b. These studies suggest that 11b should be further examined as a potentially potent clinical chemotherapeutic agent for treating pancreatic and breast cancer patients.