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 moti lity of MDA-MB-231 (human mammary cancer) cells migrating through 12-m u m pores was inhibited by DIME similar to nocodazole in a drug concen tration-and DIME structure-dependent manner. An increase of cytoplasmi c ATPase activity of DIME-treated cells without a decrease in ATP cont ents 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 cel lular mode of action of DIME is different from the action of other tox ic tubulin-targeted drugs, despite the fact that DIME in a concentrati on-dependent manner disrupts microtubule structures in intact cells.