A Novel Synthetic Indole Compound, 1,1,3-tri(3-indolyl)cyclohexane, Inhibits Microtubule Polymerization in Human Lung Cancer Cells

Abstract

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 H1437 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.