@article{APS6332,
author = {Lu Gan and Dong-xing Zhu and Li-ping Yang and Ru-shi Liu and Feng Yan and Jian Zhang},
title = {Involvement of transcription factor activator protein-2α in doxazosin-induced HeLa cell apoptosis},
journal = {Acta Pharmacologica Sinica},
volume = {29},
number = {4},
year = {2016},
keywords = {},
abstract = {Aim: To investigate the pro-apoptotic effects of α-1-adrenergic inhibitor doxazosin in HeLa cells and the potential involvement of transcription factor activator protein-2α (AP-2α) in doxazosin-induced apoptosis.
Methods: The HeLa cells were exposed to various concentrations of doxazosin for 16 h. Apoptosis was detected using a DNA fragmentation assay, Hoechst 33258 staining, and flow cytometric analysis. The expression of AP-2α and caspase-3 was detected by relative quantitative RT-PCR and Western blot assays, respectively. After the respective transfections of the HeLa cells with AP-2α overexpressing constructs and an antisense oligonucleotide against AP-2α, apoptosis was assessed by flow cytometric analysis, and the expression of AP-2α and caspase-3 was detected by relative quantitative RT-PCR and Western blot assays. The colorimetric assay was performed to detect the caspase-3 activity.
Results: Treatment with various concentrations of doxazosin for 16 h increased the apoptotic rate and total cell death rate of the HeLa cells in a dose-dependent manner and upregulated the expression of AP-2α and caspase-3 in a dose-dependent manner. A dose-dependent increase was observed in the caspase-3 activity. Overexpressing AP-2α led to the increased rate of doxazosin-induced apoptosis and the total cell death, whereas doxazosin-induced apoptosis and the total cell death in HeLa cells decreased by antisense AP-2α. Furthermore, overexpressing AP-2α increased the expression and activity of caspase-3, whereas antisense AP-2α in part abolished the increased effects of doxazosin on caspase-3 expression and activity.
Conclusion: Doxazosin induces apoptosis in HeLa cells in a dose-dependent manner, and transcription factor AP-2α is functionally involved in doxazosin-induced HeLa cell apoptosis.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/6332}
}