- Synthesis and investigation of the anticancer effects of estrone-16-oxime ethers in vitro
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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.
- Berényi, ágnes,Minorics, Renáta,Iványi, Zoltán,Ocsovszki, Imre,Ducza, Eszter,Thole, Hubert,Messinger, Josef,W?lfling, János,Mótyán, Gerg,Mernyák, Erzsébet,Frank, éva,Schneider, Gyula,Zupkó, István
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- E-ring modified steroids as novel potent inhibitors of 17β- hydroxysteroid dehydrogenase type 1
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17β-Hydroxysteroid dehydrogenases (17β-HSDs) are an important class of steroidogenic enzymes that regulate the bioavailability of active estrogens and androgens and are as yet a relatively unexploited therapeutic target. Based on our investigations and th
- Fischer, Delphine S.,Allan, Gillian M.,Bubert, Christian,Vicker, Nigel,Smith, Andrew,Tutill, Helena J.,Purohit, Atul,Wood, Lynn,Packham, Graham,Mahon, Mary F.,Reed, Michael J.,Potter, Barry V. L.
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p. 5749 - 5770
(2007/10/03)
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- D-ring modified estrone derivatives as novel potent inhibitors of steroid sulfatase
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A series of novel D-ring modified derivatives of estrone was synthesized and tested as inhibitors of steroid sulfatase (STS). The steroidal D-ring was cleaved via an iodoform reaction and thermal condensation of the resulting marrianolic acid derivative g
- Fischer, Delphine S.,Woo, L. W. Lawrence,Mahon, Mary F.,Purohit, Atul,Reed, Michael J.,Potter, Barry V. L.
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p. 1685 - 1700
(2007/10/03)
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