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

Hui Wang, Yan Ye, Jian Hong Chu, Guo Yuan Zhu, David W F FONG, Zhiling YU*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)160-167
Number of pages8
JournalIntegrative Cancer Therapies
Volume10
Issue number2
DOIs
Publication statusPublished - Jun 2011

Scopus Subject Areas

  • Oncology
  • Complementary and alternative medicine

User-Defined Keywords

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

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