Evaluation of the anticancer action of a permanently charged tamoxifen derivative, tamoxifen methiodide: an MRI study

Abstract

The anticancer action of a permanently charged tamoxifen derivative, tamoxifen methiodide (TMI), was assessed in a model of breast cancer. In addition, analysis of MCF-7 cells in cultures was performed to consider the anticancer mechanism of TMI. Nude mice were implanted with MCF-7 human cancer cells in the ventral fat pad at the level of the milkline (breast). The effect of TMI (administered as a slow-release pellet) and placebo were evaluated using magnetic resonance imaging (MRI) as well as by histological evaluation. The action of TMI and tamoxifen on cell growth of MCF-7 cells in cultures was also assessed. TMI induced tumor regression, while placebo-treated animals manifested tumor masses that grew monotonically throughout the experimental period (25 days). MRI revealed and histopathology confirmed that TMI treatment resulted in tumor necrosis which (1) had a faster onset; (2) was more extensive; and (3) was more intense than that observed by partial estrogen ablation (placebo-treated animals). Studies with MCF-7 cells in culture suggested that tamoxifen and TMI are equipotent in vitro. Given various reports that TMI is more potent than tamoxifen in vivo and that the anticancer efficacy between TMI and tamoxifen cannot be explained by differences in estrogen receptor interaction or effects on MCF-7S cell in culture, other mechanism may differentially contribute to the anticancer action of TMI.