Szumilak Marta, Galdyszynska Malgorzata, Dominska Kamila, Stanczak Andrzej, Piastowska-Ciesielska Agnieszka
Department of Hospital Pharmacy, Faculty of Pharmacy, Medical University of Lodz, Łódź, Poland.
Department of Comparative Endocrinology, Medical University of Lodz, Łódź, Poland.
Acta Biochim Pol. 2017;64(2):307-313. doi: 10.18388/abp.2016_1416. Epub 2017 Apr 14.
The aim of this study was to expand our knowledge about anticancer activity of some polyamine derivatives with quinoline or chromane as terminal moieties. Tested compounds were evaluated in vitro towards metastatic human prostate adenocarcinoma (PC3), human carcinoma (DU145) and mammary gland adenocarcinoma (MCF7) cell lines. Cell viability was estimated on the basis of mitochondrial metabolic activity using water-soluble tetrazolium WST1 to establish effective concentrations of the tested compounds under experimental conditions. Cytotoxic potential of polyamine derivatives was determined by the measurement of lactate dehydrogenase activity released from damaged cells, changes in mitochondrial membrane potential, the cell cycle distribution analysis and apoptosis assay. It was revealed that the tested polyamine derivatives differed markedly in their antiproliferative activity. Bischromane derivative 5a exhibited a rather cytostatic than cytotoxic effect on the tested cells, whereas quinoline derivative 3a caused changes in cell membrane integrity, inhibited cell cycle progression, as well as induced apoptosis of prostate and breast cancer cells which suggest its potential application in cancer therapy.
本研究的目的是拓展我们对一些以喹啉或色满为末端基团的多胺衍生物抗癌活性的认识。对测试化合物针对转移性人前列腺腺癌（PC3）、人癌（DU145）和乳腺腺癌（MCF7）细胞系进行了体外评估。基于线粒体代谢活性，使用水溶性四唑盐WST1来估计细胞活力，以确定实验条件下测试化合物的有效浓度。通过测量受损细胞释放的乳酸脱氢酶活性、线粒体膜电位变化、细胞周期分布分析和凋亡检测来确定多胺衍生物的细胞毒性潜力。结果表明，测试的多胺衍生物在其抗增殖活性方面有显著差异。双色满衍生物5a对测试细胞表现出相当的细胞生长抑制作用而非细胞毒性作用，而喹啉衍生物3a导致细胞膜完整性改变，抑制细胞周期进程，并诱导前列腺和乳腺癌细胞凋亡，这表明其在癌症治疗中的潜在应用价值。
