Proteomic identification of proteins involved in the anticancer activities of oridonin in HepG2 cells.
Oridonin is the main bioactive constituent of the Chinese medicinal herb Isodon rubescens and has been shown to have anti-neoplastic effects against a number of cancers in vitro and in vivo. Here we report the proteomic identification of proteins involved in the anticancer properties of oridonin in hepatocarcinoma HepG2 cells. Cell viability assay showed that oridonin dose-dependently inhibited cell growth with an IC(50) of 41.77μM. Treatment with oridonin at 44μM for 24h induced apoptosis and G2/M cell cycle arrest, which were associated with nine differentially expressed proteins identified by proteomic analysis. The proteomic expression patterns of Hsp70.1, Sti1 and hnRNP-E1 were confirmed by quantitative real-time PCR and/or immunoblotting. Eight of the nine identified proteins are shown, for the first time, to be involved in the anticancer activities of oridonin. Up-regulation of Hsp70.1, STRAP, TCTP, Sti1 and PPase, as well as the down-regulation of hnRNP-E1 could be responsible for the apoptotic and G2/M-arresting effects of oridonin observed in this study. Up-regulation of HP1 beta and GlyRS might contribute to inhibitory effects of oridonin on telomerase and tyrosine kinase, respectively. These findings shed new insights into the molecular mechanisms underlying the anticancer properties of oridonin in liver cancer cells.
Wang
Hui
H
Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
Ye
Yan
Y
Pan
Si-Yuan
SY
Zhu
Guo-Yuan
GY
Li
Ying-Wei
YW
Fong
David W F
DW
Yu
Zhi-Ling
ZL
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D037602:Isodon / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D040901:Proteomics / Q000379:methods; D000090324:Tumor Protein, Translationally-Controlled 1
D000972:Antineoplastic Agents, Phytogenic; D045786:Diterpenes, Kaurane; D009363:Neoplasm Proteins; D010936:Plant Extracts; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; C011959:oridonin