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Proteomic analysis reveals tanshinone IIA enhances apoptosis of advanced cervix carcinoma C a S ki cells through mitochondria intrinsic and endoplasmic reticulum stress pathways
Author(s) -
Pan TaiLong,
Wang PeiWen,
Hung YuChiang,
Huang ChunHsun,
Rau KunMing
Publication year - 2013
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201300274
Subject(s) - unfolded protein response , apoptosis , endoplasmic reticulum , cancer research , paclitaxel , programmed cell death , cancer cell , kinase , signal transduction , chemistry , cancer , phosphorylation , cell culture , p38 mitogen activated protein kinases , microbiology and biotechnology , protein kinase a , biology , medicine , biochemistry , genetics
Cervix cancer is the second most common cancer among women worldwide, whereas paclitaxel, the first line chemotherapeutic drug used to treat cervical cancer, shows low chemosensitivity on the advanced cervical cancer cell line. Tanshinone IIA (Tan IIA) exhibited strong growth inhibitory effect on CaSki cells (IC 50 = 5.51 μM) through promoting caspase cascades with concomitant upregulating the phosphorylation of p38 and JNK signaling. Comprehensive proteomics revealed the global protein changes and the network analysis implied that Tan IIA treatment would activate ER stress pathways that finally lead to apoptotic cell death. Moreover, ER stress inhibitor could alleviate Tan IIA caused cell growth inhibition and ameliorate C/EBP‐homologous protein as well as apoptosis signal‐regulating kinase 1 mediated cell death. The therapeutic interventions targeting the mitochondrial‐related apoptosis and ER stress responses might be promising strategies to conquer paclitaxel resistance.