Inhibition of migration of MDA-MB-231 cells by methyl-3,5-diiodo-4-(4'-methoxyphenoxy)benzoate (DIME)

The GTPase activity of purified dimeric tubulin (alpha+beta) at 5 mu M was insensitive to methyl-3,5-diiodo-4-(4'-methoxyphenoxy) benzoate (DIME), in contrast to nocodazole which activated GTPase. Cellular motility of MDA-MB-231 (human mammary cancer) cells migrating through 12-mu m pores was inhibited by DIME similar to nocodazole in a drug concentration-and DIME structure-dependent manner. An increase of cytoplasmic ATPase activity of DIME-treated cells without a decrease in ATP contents of intact cells suggests that DIME may also influence additional as yet unidentified ATP-dependent system(s) probably also involved in cell motility. These results show that DIME not only arrests cells in M phase but also inhibits cell motility in interphase. However the cellular mode of action of DIME is different from the action of other toxic tubulin-targeted drugs, despite the fact that DIME in a concentration-dependent manner disrupts microtubule structures in intact cells.