Bognar Zita, Fekete Katalin, Bognar Rita, Szabo Aliz, Vass Reka A, Sumegi Balazs
a Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary.
b Department of Anatomy, University of Pécs Medical School, Pécs, Hungary.
Can J Physiol Pharmacol. 2018 Oct;96(10):1004-1011. doi: 10.1139/cjpp-2018-0113. Epub 2018 May 30.
Previously, we found that desethylamiodarone (DEA) may have therapeutic potentiality in bladder cancer. In this study, we determined its effects on human cervical cancer cells (HeLa). Cell viability was evaluated by Muse Cell Count & Viability Assay; cell apoptosis was detected by Muse Annexin V & Dead Cell Assay. Cell cycle was flow cytometrically determined by Muse Cell Cycle Kit and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33342 staining. The changes in the expression levels of apoptosis-related proteins in the HeLa cells were assessed by immunoblot. Our results showed that DEA significantly inhibited the proliferation and viability of HeLa cells and induced apoptosis in vitro in dose-dependent and also in cell cycle-dependent manner because DEA induced G0/G1 phase arrest in the HeLa cell line. We found that DEA treatment downregulated the expression of phospho-Akt and phospho-Bad. In addition, DEA could downregulate expression of Bcl-2, upregulate Bax, and induce cytochrome c release. Our results indicate that DEA might have significance as an anti-tumor agent against human cervical cancer.
此前，我们发现去乙基胺碘酮（DEA）可能在膀胱癌中具有治疗潜力。在本研究中，我们测定了其对人宫颈癌细胞（HeLa）的作用。通过Muse细胞计数与活力测定法评估细胞活力；通过Muse膜联蛋白V与死细胞测定法检测细胞凋亡。使用Muse细胞周期试剂盒通过流式细胞术测定细胞周期，并在Hoechst 33342染色后在荧光显微镜下观察细胞的形态变化。通过免疫印迹评估HeLa细胞中凋亡相关蛋白表达水平的变化。我们的结果表明，DEA显著抑制HeLa细胞的增殖和活力，并在体外以剂量依赖性和细胞周期依赖性方式诱导凋亡，因为DEA诱导HeLa细胞系停滞于G0/G1期。我们发现DEA处理下调了磷酸化Akt和磷酸化Bad的表达。此外，DEA可下调Bcl-2的表达，上调Bax的表达，并诱导细胞色素c释放。我们的结果表明，DEA作为一种抗人宫颈癌的抗肿瘤药物可能具有重要意义。
