Inhibition of cellular chemotactic invasion by a vinca alkaloid, conophylline

Abstract

K-ras-NIH3T3 cells were more invasive than NIH3T3 cells in a chemotactic invasion assay. Conophylline, a new vinca alkaloid isolated as a ras function inhibitor, inhibited the invasion of K-ras-NIH3T3 cells, while it showed no effect on NIH3T3 cells. Conophylline did not increase expression of fibronectin but induced E-cadherin expression in K-ras-NIH3T3 cells. Mouse melanoma B16/F10 is a highly metastatic cell line. Conophylline was found to induce flat morphology in B16/F10 cells and it again inhibited the invasion of the cells to the matrigel membrane. It induced fibronectin expression but not E-cadherin expression in B 16/F10 cells. Thus, conophylline lowered invasiveness of K-ras-NIH3T3 and B 16/F10 cells by reversing neoplastic phenotypes.