Open AccessOridonin induces apoptosis via PI3K/Akt pathway in cervical carcinoma HeLa cell line 1
Author(s) -
HU Hongzhen,
YANG Yuebo,
XU Xiangdong,
SHEN Hongwei,
SHU Yimin,
REN Zi,
LI Xiaomao,
SHEN Huiming,
ZENG Haitao
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00667.x
Subject(s) - hela , apoptosis , protein kinase b , microbiology and biotechnology , pi3k/akt/mtor pathway , cell growth , biology , cell culture , programmed cell death , chemistry , biochemistry , genetics
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.