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新型喹诺酮7-乙基-9-乙基-6-氧代-6,9-二氢[1,2,5]硒二唑并[3,4-h]喹啉-7-羧酸酯对人宫颈癌HeLa细胞系单独作用及联合紫外线A照射时的促凋亡作用

Pro-apoptotic effect of new quinolone 7- ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo [3,4-h]quinoline-7-carboxylate on cervical cancer cell line HeLa alone/with UVA irradiation.

作者信息

Jantová Soňa, Mrvová Nataša, Hudec Roman, Sedlák Ján, Pánik Miroslav, Milata Viktor

机构信息

Institute of Biochemistry, Nutrition and Health Protection, Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovak Republic.

Institute of Biochemistry, Nutrition and Health Protection, Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovak Republic; Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic.

出版信息

Toxicol In Vitro. 2016 Jun;33:35-44. doi: 10.1016/j.tiv.2016.02.012. Epub 2016 Feb 23.

Abstract

7- ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo [3,4-h]quinoline-7-carboxylate (E2h) is a new synthetically prepared quinolone derivative, which in our primary study showed cytotoxic effects towards tumor cells. The aim of the present study was to examine the antiproliferative and apoptosis inducing activities of E2h towards human cervical cancer cell line HeLa with/without the presence of UVA irradiation. Further, the molecular mechanism involved in E2h-induced apoptosis in HeLa cells was investigated. Our results showed that both non-photoactivated and photoactivated E2h caused morphological changes and inhibited the cell growth of HeLa cells in a time- and dose-dependent manner. Irradiation increased the sensitivity of HeLa cells to E2h. Quinolone induced S and G2/M arrest and apoptosis in HeLa cells, as characterized by DNA fragmentation and flow cytometry. In addition, E2h elevated the level of reactive oxygen species and activated caspases 3. In conclusions, E2h alone/in combination with UVA irradiation induced apoptosis in HeLa cells through the ROS-mitochondrial/caspase 3-dependent pathway.

摘要

7-乙基-9-乙基-6-氧代-6,9-二氢[1,2,5]硒二唑并[3,4-h]喹啉-7-羧酸酯(E2h)是一种新合成的喹诺酮衍生物,在我们的初步研究中显示对肿瘤细胞具有细胞毒性作用。本研究的目的是研究E2h在有无UVA照射情况下对人宫颈癌细胞系HeLa的抗增殖和诱导凋亡活性。此外,还研究了E2h诱导HeLa细胞凋亡的分子机制。我们的结果表明,非光活化和光活化的E2h均导致形态学变化,并以时间和剂量依赖性方式抑制HeLa细胞的生长。照射增加了HeLa细胞对E2h的敏感性。喹诺酮诱导HeLa细胞发生S期和G2/M期阻滞以及凋亡,其特征为DNA片段化和流式细胞术检测结果。此外,E2h提高了活性氧水平并激活了半胱天冬酶3。总之,E2h单独使用/与UVA照射联合使用通过ROS-线粒体/半胱天冬酶3依赖性途径诱导HeLa细胞凋亡。

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