title: Induction of apoptosis and downregulation of ERα in DMBA-induced mammary gland tumors in Sprague-Dawley rats by synthetic 3,5-disubstituted isoxazole derivatives.
abstract: 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 µM, 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 ERα protein expression was evaluated by immunohistochemistry, which showed tumor regression and downregulation of ERα in tumor cells. The present results implicate that compound 2b could be used for the further derivatization for the treatment of breast cancer.
authors.affiliation: Department of Studies in Chemistry, Manasagangotri University of Mysore, Mysore, 570006, India.
authors.forename: Hanumappa
authors.initials: H
authors.lastname: Ananda
authors.affiliation: Department of Chemistry, Regional Institute of Education (NCERT, New Delhi), Manasagangotri, Mysore, 570006, India.
authors.forename: Kothanahally S Sharath
authors.initials: KS
authors.lastname: Kumar
authors.affiliation: Department of Studies in Chemistry, Manasagangotri University of Mysore, Mysore, 570006, India.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Hegde
authors.affiliation: Department of Studies in Chemistry, Manasagangotri University of Mysore, Mysore, 570006, India. rangappaks@gmail.com.
authors.forename: Kanchugarakoppal S
authors.initials: KS
authors.lastname: Rangappa
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000737:Androstenols / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000737:Androstenols; D047628:Estrogen Receptor alpha; D009363:Neoplasm Proteins; C017039:azastene; D015127:9,10-Dimethyl-1,2-benzanthracene
keywords: Apoptosis; Cytotoxicity; Dimethylbenzanthracene (DMBA); Estrogen receptor alpha (ERα); Isoxazoles