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Induction of apoptosis and downregulation of ERalpha in DMBA-induced mammary gland tumors in Sprague?Dawley rats by synthetic 3,5-disubstituted isoxazole derivatives
Isoxazole derivatives are an important group of chemotherapeutic prototypes. In the current study, we have synthesized few isoxazole derivatives and tested them for their antiproliferative properties in cancer cell lines such as MCF7 and HeLa. The lead compound, 3-(3,4-dimethoxyphenyl)-5-(thiophen-2-yl)isoxazole (2b), showed considerable inhibition of proliferation of MCF7 and HeLa cells with the IC50 values of 19.5 and 39.2?muM, respectively. Cell cycle analyses and annexin-FITC staining in 2b-treated breast adenocarcinoma cells (MCF7) showed increased sub-G1 population and apoptosis. Furthermore, we tested the tumor inhibitory effect of 2b and estrogen receptor expression profile in DMBA-induced mammary tumors in Sprague?Dawley rats. The gross morphology of tumor studies was investigated by histopathology and ERalpha protein expression was evaluated by immunohistochemistry, which showed tumor regression and downregulation of ERalpha in tumor cells. The present results implicate that compound 2b could be used for the further derivatization for the treatment of breast cancer.
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Reference£º
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem