Open AccessImplication of 14‐3‐3ε and 14‐3‐3θ/τ in proteasome inhibition‐induced apoptosis of glioma cells
Author(s) -
Yan Ying,
Xu Ying,
Gao YanYan,
Zong ZhiHong,
Zhang Qiang,
Li Chao,
Wang HuaQin
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12033
Subject(s) - mg132 , glioma , apoptosis , proteasome , cancer research , downregulation and upregulation , proteasome inhibitor , cytotoxicity , biology , chemistry , microbiology and biotechnology , in vitro , biochemistry , gene
Proteasome inhibitors represent a novel class of anticancer agents that are used in the treatment of hematologic malignancies and various solid tumors. However, mechanisms underlying their anticancer actions were not fully understood. It has been reported that strong 14‐3‐3 protein expression is observed and associated with tumor genesis and progression of astrocytoma. In addition, global inhibition of 14‐3‐3 functions with a general 14‐3‐3 antagonist difopein induces apoptosis of human astrocytoma cells, validating 14‐3‐3 as a potential molecular target for anticancer therapeutic management. In the current study, for the first time we demonstrated that proteasome inhibitors downregulated 14‐3‐3ε and 14‐3‐3θ/τ in U87 and SF 295 glioma cells. Overexpression of 14‐3‐3ε and 14‐3‐3θ/τ significantly suppressed apoptosis of human glioma cells induced by proteasome inhibitors. We also demonstrated that MG 132 activated ASK 1 and si ASK 1 compromised the MG 132‐induced apoptosis of glioma cells. Furthermore, overexpression of 14‐3‐3ε and 14‐3‐3θ/τ markedly suppressed activation of ASK 1. Collectively, the current study supported that proteasome inhibitors, at least in part, caused cytotoxicity of glioma cells via downregulation of 14‐3‐3ε and 14‐3‐3θ/τ and subsequent activation of ASK 1. ( Cancer Sci 2013; 104: 55–61)