http://dx.doi.org/10.1177/1534735410383171">
 

Document Type

Journal Article

Department/Unit

School of Chinese Medicine

Title

Proteomic and functional analyses reveal the potential involvement of endoplasmic reticulum stress and α-CP1 in the anticancer activities of oridonin in HepG2 cells

Language

English

Abstract

Oridonin has been shown to exhibit therapeutic effects against hepatocellular carcinoma (HCC) in vitro and in vivo. This study aimed to identify the anti-HCC mechanisms of oridonin in HepG2 cells using proteomic and functional analyses. MTT assay showed that oridonin treatment for 24 hours dose-dependently inhibited cell growth with an IC 50 value of 40.4 μM. Treatment with 40 μM oridonin for 24 hours induced apoptosis determined by nuclear morphologic changes of DAPI-stained cells and flow cytometric analysis of annexin V-FITC/PI-stained cells, which was accompanied by Grp78 upregulation and α-CP1 downregulation identified by proteomic analysis. Immunoblot analysis for the endoplasmic reticulum (ER) stress- related proteins demonstrated that the expression levels of phosphorylated PERK (p-PERK) and CHOP were increased, whereas PERK, ATF-6, and IRE-1 expression levels were decreased. Knockdown of α-CP1 expression with siRNA significantly increased cell death and apoptosis in control and oridonin-treated HepG2 cells. Together, these data provide proteomic and functional evidence for the potential involvement of ER stress and α-CP1 in the antiproliferative and apoptotic activities of oridonin in HepG2 cells, which shed new light on the action mechanisms of oridonin in HCC management. © The Author(s) 2011.

Keywords

α-CP1, apoptosis, ER stress, Grp78, oridonin, proteomics

Publication Date

2011

Source Publication Title

Integrative Cancer Therapies

Volume

10

Issue

2

Start Page

160

End Page

167

Publisher

SAGE Publications

ISSN (print)

15347354

ISSN (electronic)

1552695X

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