Please use this identifier to cite or link to this item: http://rportal.lib.ntnu.edu.tw:80/handle/77345300/7150
Title: A Novel Synthetic Indole Compound, 1, 1, 3-tri(3-indolyl)Cyclohexane, Inhibits Microtubule Polymerization in Human Lung Cancer Cells
Other Titles: 新穎的1, 1, 3-tri(3-indolyl)cyclohexane 抑制肺癌細胞株 microtubule 微管聚合作用探討
Authors: 李慶孝
姚清發
李桂楨
王憶卿
Issue Date: Dec-2008
Publisher: 國立臺灣師範大學生命科學學系
Department of Life Science, NTNU
Abstract: 目的:肺癌在世界各地無論男性或女性都是發病率、死亡率名列前茅的惡性腫瘤。因此,發現與合成新穎的肺癌治療抗癌藥物是刻不容緩的工作。 材料與方法:本研究團隊發展了一種新穎的吲哚結構合成化合物1, 1, 3-tri(3-indolyl)cyclohexane(3-indole),並藉由A549及H1437人類肺癌細胞株來探討新穎抗癌藥物對於肺癌細胞的毒殺作用及其機制。 結果:新穎的抗癌藥物3-indole可以抑制A549和H1437肺癌細胞株細胞生長並誘導細胞週期停滯在G2-M期。在IMR90正常肺細胞內,3-indole無法抑制其細胞生長,且細胞骨架microtubule微管為呈現網狀之完整分佈於整個細胞體內;而經由免疫細胞染色法發現3-indole處理A549細胞後,其microtubule微管網絡可見到幾乎受到破壞且聚集於細胞核周圍,無法順利延伸散佈於整個細胞體內。此外,西方墨點法分析顯示3-indole處理可抑制A549細胞microtubule微管聚合作用並呈現劑量相關性。 結論:3-indole具有抑制A549和H1437肺癌細胞株細胞生長及抑制A549肺癌細胞株細胞骨架microtubule微管聚合作用,顯示具有發展作為新穎的抗微管作用癌症用藥的價值。
BACKGROUND. Lung cancer is the most common malignancies in both men and women worldwide. Thus, the development of more effective anti-cancer drugs for lung cancer is urgently needed. METHODS. We generated a novel indole compound, 1,1,3-tri(3-indolyl)cyclohexane (3-indole), with high purity and in large quantities. 3-indole was tested for its biological activity in A549 and Hl437 lung cancer cells. RESULTS. Our data indicated that 3-indole caused a concentration-dependent reduction in cell proliferation in human lung cancer cells but not in the normal lung cells. In addition, 3-indole induced G2-M cell cycle arrest in A549 and H1437 lung cancer cells to different extents. Using immunochemistry assay, the DMSO-treated control was shown to exhibit normal filamentous arrangement and organization of microtubule network whereas in A549 cells treated with 3-indole, almost complete loss of cellular microtubule networks throughout the cytoplasm was observed. Moreover, Western blot data showed that 3-indole dose-dependently inhibited microtubule polymerization in A549 cells. CONCLUSIONS. Based on its potent cell growth inhibition in lung cancer cell models, our data suggest that this novel synthetic 3-indole compound of high purity and yield is a potential antimicrotubule polymerization agent for cancer treatment.
URI: http://rportal.lib.ntnu.edu.tw//handle/77345300/7150
Other Identifiers: F0793C1E-187D-247A-8A61-E482F036D610
Appears in Collections:生物學報

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