Marczak Agnieszka, Denel-Bobrowska Marta, Łukawska Małgorzata, Oszczapowicz Irena
Department of Thermobiology, Institute of Biophysics, Faculty of Biology and Environmental Protection, Lodz University Pomorska, Lodz, Poland.
Department of Modified Antibiotics, Institute of Biotechnology and Antibiotics, Warsaw, Poland
Anticancer Res. 2015 Apr;35(4):1935-40.
BACKGROUND/AIM: The ability of five formamidinodoxorubicins to induce apoptosis of MCF-7 breast cancer cells was tested. All these compounds were modified at C-3' and contain a formamidine group (-N=CH-NRR), with the rest of the cyclic secondary amine (HNRR) of a gradually increasing ring size.
Cytotoxicity was assessed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. To analyze apoptosis, double staining using fluorescence probes Hoechst 33258/propidium iodide (PI) and annexin V- Fluorescein isothiocyanate/PI was carried-out. Additionally, the TdT-mediated dUTP nick-end labelling test and activity of caspase 3 were determined.
The four tested derivatives displayed a significant increase in antiproliferative activity in comparison to doxorubicin. All of the tested derivatives induced caspase-dependent apoptosis of MCF-7 cells.
DOX-F MOR and DOX-F PAZ analogs are more potent apoptosis inducers than doxorubicin.
背景/目的：测试了五种甲脒基阿霉素诱导MCF - 7乳腺癌细胞凋亡的能力。所有这些化合物均在C-3'位进行了修饰，并含有一个甲脒基（-N=CH-NRR），其环状仲胺（HNRR）的其余部分环大小逐渐增加。
使用3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴盐法评估细胞毒性。为了分析细胞凋亡，使用荧光探针Hoechst 33258/碘化丙啶（PI）和膜联蛋白V - 异硫氰酸荧光素/PI进行双重染色。此外，还进行了TdT介导的dUTP缺口末端标记试验和半胱天冬酶3的活性测定。
与阿霉素相比，四种测试衍生物的抗增殖活性显著增加。所有测试衍生物均诱导MCF - 7细胞发生半胱天冬酶依赖性凋亡。
DOX - F MOR和DOX - F PAZ类似物比阿霉素更有效地诱导细胞凋亡。
