title: Synthesis and investigation of the anticancer effects of estrone-16-oxime ethers in vitro.
abstract: An expanding body of evidence indicates the possible role of estrane derivatives as useful anticancer agents. The aim of this study was to describe the cytotoxic effects of 63 newly synthetized estrone-16-oxime ethers on human cancer cell lines (cervix carcinoma HeLa, breast carcinoma MCF7 and skin epidermoid carcinoma A431), studied by means of the MTT assay. Four of the most promising compounds were selected for participation in additional experiments in order to characterize the mechanism of action, including cell cycle analysis, morphological study and the 5-bromo-2'-deoxyuridine incorporation assay. The cancer selectivity was tested on a noncancerous fibroblast cell line (MRC-5). Since apoptosis and cell cycle disturbance were observed, caspase-3 activities were further assayed for the two most effective agents. These estrone-16-oxime analogs activated caspase-3 and changed the mRNA level expression of endogenous factors regulating the G1-S phase transition (retinoblastoma protein, CDK4 and p16). The repression of retinoblastoma protein was reinforced at a protein level too. These experimental data lead to the conclusion that estrone-16-oxime ethers may be regarded as potential starting structures for the design of novel anticancer agents.
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Berényi
authors.forename: Renáta
authors.initials: R
authors.lastname: Minorics
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Iványi
authors.forename: Imre
authors.initials: I
authors.lastname: Ocsovszki
authors.forename: Eszter
authors.initials: E
authors.lastname: Ducza
authors.forename: Hubert
authors.initials: H
authors.lastname: Thole
authors.forename: Josef
authors.initials: J
authors.lastname: Messinger
authors.forename: János
authors.initials: J
authors.lastname: Wölfling
authors.forename: Gergő
authors.initials: G
authors.lastname: Mótyán
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Mernyák
authors.forename: Éva
authors.initials: É
authors.lastname: Frank
authors.forename: Gyula
authors.initials: G
authors.lastname: Schneider
authors.forename: István
authors.initials: I
authors.lastname: Zupkó
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication; D004354:Drug Screening Assays, Antitumor; D004970:Estrone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D004987:Ethers / Q000138:chemical synthesis / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D010091:Oximes / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004987:Ethers; D010091:Oximes; D004970:Estrone; C505407:CASP3 protein, human; D053148:Caspase 3