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  • Title: Antitumor activity of a novel antiestrogen (Analog II) on human breast cancer cells.
    Author: Jain PT, Rajah TT, Pento JT.
    Journal: Anticancer Drugs; 1997 Nov; 8(10):964-73. PubMed ID: 9436640.
    Abstract:
    Analog II (1,1-dichloro-cis-2,3-diarylcyclopropane), previously shown to be a pure antiestrogen in mice, was examined for potential antitumor activity on human breast cancer cells in culture. In this study, Analog II produced a dose-related antiproliferative effect on the growth of estrogen receptor (ER)-positive MCF-7 human breast cancer cells over a concentration range of 10(-11) to 10(-5) M. Analog II increased the fraction of MCF-7 cells in the G2/M phase of the cell cycle. Further, this compound inhibited the growth of ER-negative MDA-MB-231 human breast cancer cells over a concentration range of 10(-9) to 10(-6) M. Using scanning electron microscopy to evaluate drug-induced changes in cellular morphology, it was observed that Analog II decreased the length and density of microvilli on both MCF-7 and MDA-MB-231 cells. The effects of Analog II on MCF-7 and MDA-MB-231 cell proliferation and morphology were not reversed in the presence of estradiol. In addition, the induction of estrogen-dependent genes in MCF-7 cells was not reversed by Analog II. It was observed that non-specific cytotoxicity may be responsible for part of the Analog II-induced inhibition on MCF-7 and MDA-MB-231 cell proliferation. However, the antitumor activity of this compound was found to be specific to human breast cancer cells since it did not alter the proliferation or viability of non-breast A-549 human lung cancer cells. In conclusion, these results indicate that Analog II is a potent antitumor agent, has a unique antitumor mechanism in breast cancer cells and may be effective in the treatment of breast cancer.
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