Inhibition of cellular chemotactic invasion by a vinca alkaloid, conophylline.
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.
Amino
N
N
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Ohse
T
T
Koyano
T
T
Umezawa
K
K
D016475:3T3 Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015820:Cadherins / Q000096:biosynthesis; D002633:Chemotaxis / Q000187:drug effects*; D005353:Fibronectins / Q000096:biosynthesis; D011905:Genes, ras; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D014748:Vinca Alkaloids / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D005353:Fibronectins; D014748:Vinca Alkaloids; C099167:conophylline