Molecular pharmacology of methyl-3,5-diiodo-4 (4'methoxyphenoxy) benzoate (DIME) and its non-hydrolyzible ethanone analog (DIPE) (Review)

Abstract

A molecular structural relationship of thyroid hormones to methyl-3,5-diiodo-4-(4'-methoxy-phenoxy) benzoate (DIME) and 1-[3,5-diiodo-4-(4'-methoxyphenoxy)-phenyl]-ethanone) (DIPE) and to apoptosis-mediated metamorphogenic mechanisms is postulated. DIME disrupts microtubule assembly already in anaphase, preparing cells for G2/M block, chromosome aggregation and caspase-3 mediated apoptosis. Cooperative action of DIME and vincristine, defining mutually exclusive cellular sites, identifies microtubules as primary drug targets followed by downstream cellular consequences, leading to cell death. Absence of in vivo toxicity of DIME appears to be related to impermeability to DIME of normal cells, but not of tumor cells in vivo. Normal tissue cells hydrolyze DIME but most tumor cells, except lung cancer cells, do not. DIPE, being resistant to enzymatic hydrolysis, is equally effective in all tumor cells.