Synthesis and investigation of the anticancer effects of estrone-16-oxime ethers in vitro

被引：55

作者：

Berenyi, Agnes ^{[1
]}

Minorics, Renata ^{[1
]}

Ivanyi, Zoltan ^{[2
]}

Ocsovszki, Imre ^{[3
]}

Ducza, Eszter ^{[1
]}

Thole, Hubert ^{[2
]}

Messinger, Josef ^{[2
]}

Woelfling, Janos ^{[2
]}

Motyan, Gergo ^{[2
]}

Mernyak, Erzsebet ^{[2
]}

Frank, Eva ^{[2
]}

Schneider, Gyula ^{[2
]}

Zupko, Istvan ^{[1
]}

机构：

[1] Univ Szeged, Dept Pharmacodynam & Biopharm, H-6720 Szeged, Hungary

[2] Univ Szeged, Dept Organ Chem, H-6720 Szeged, Hungary

[3] Univ Szeged, Dept Biochem, H-6720 Szeged, Hungary

来源：

STEROIDS | 2013年 / 78卷 / 01期

基金：

匈牙利科学研究基金会;

关键词：

Estrone-16-oxime ethers; Cell viability; Apoptosis; Cell cycle blockade; CELL-CYCLE ARREST; ORAL; 2-METHOXYESTRADIOL; APOPTOSIS; DIOSGENIN; GROWTH; EXPRESSION; INDUCTION; PROLIFERATION; ACTIVATION; ANALOGS;

D O I：

10.1016/j.steroids.2012.10.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (c) 2012 Elsevier Inc. All rights reserved.

引用

页码：69 / 78

页数：10

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