1. Oridonin induces apoptosis via PI3K/Akt pathway in cervical carcinoma HeLa cell line.
- Author
-
Hong-zhen Hu, Yue-bo Yang, Xiang-dong Xu, Hong-wei Shen, Zi Ren, Xiao-mao Li, Hui-ming Shen, Hai-tao Zeng, and Yi-min Shu
- Subjects
APOPTOSIS ,CERVICAL cancer ,HELA cells ,CHROMATIN ,STAINS & staining (Microscopy) ,FLOW cytometry ,WESTERN immunoblotting - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF