@article{APS3672,
author = {Hong-zhen Hu and Yue-bo Yang and Xiang-dong Xu and Hong-wei Shen and Yi-min Shu and Zi Ren and Xiao-mao Li and Hui-ming Shen and Hai-tao Zeng},
title = {Oridonin induces apoptosis via PI3K/Akt pathway in cervical carcinoma HeLa cell line},
journal = {Acta Pharmacologica Sinica},
volume = {28},
number = {11},
year = {2016},
keywords = {},
abstract = {Aim: To investigate the apoptosis-inducing effect of oridonin, a diterpenoid isolated from Rabdosia rubescens, in the human cervical carcinoma HeLa cell line.
Methods: A morphological analysis, nuclear condensation, and fragmentation of chromatin were monitored using Hoechst 33342 staining. Cell viability was assessed using the 3-(4, 5-dimethylthiazol-(2)-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis and the apoptosis-related activation in the HeLa cell line were evaluated by flow cytometry and Western blotting.
Results: Oridonin suppressed the proliferation of the HeLa cell line in a dose- and time-dependent fashion. Oridonin treatment downregulated the activation of protein kinase B (Akt), the expression of forkhead box class O (FOXO) transcription factor, and glycogen synthase kinase 3 (GSK3). Oridonin also induced the release of cytochrome c accompanied by the activation of caspase-3 and poly-adenosine diphosphate-ribose polymerase cleavage. In addition, Z-D(OMe)-E(OMe)-V-D(OMe)-FMK (z-DEVD-fmk), an inhibitor of caspases, prevented caspase-3 activation and abrogated oridonin-induced cell death. Finally, oridonin treatment of the HeLa cell line downregulated the expression of the inhibitor of the apoptosis protein.
Conclusion: Our results showed that oridonin-induced apoptosis involved several molecular pathways. Oridonin may suppress constitutively activated targets of phosphatidylinositol 3-kinase (Akt, FOXO, and GSK3) in the HeLa cell line, inhibiting the proliferation and induction of caspase-dependent apoptosis.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/3672}
}