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Inhibition of JNK3 Promotes Apoptosis Induced by BH3 Mimetic S1 in Chemoresistant Human Ovarian Cancer Cells
Author(s) -
Yang Xiaochun,
Xiang Xiyan,
Xia Meihui,
Su Jing,
Wu Yao,
Shen Luyan,
Xu Ye,
Sun Liankun
Publication year - 2015
Publication title -
the anatomical record
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.22991
Subject(s) - unfolded protein response , apoptosis , endoplasmic reticulum , microbiology and biotechnology , downregulation and upregulation , autophagy , programmed cell death , kinase , cancer research , chemistry , cell culture , ovarian cancer , biology , cancer , biochemistry , gene , genetics
ABSTRACT Previous studies have suggested that the novel BH3 mimetic S1 could induce apoptosis in diverse tumor cell lines through endoplasmic reticulum (ER) stress or mitochondrial cell death pathways. The activation of c‐Jun N‐terminal kinase (JNK) through inositol requiring enzyme‐1 (IRE1) is closely connected to ER stress‐induced apoptosis. However, the role of JNK is complex, as there are different JNK subtypes and the function of each subtype is still not entirely clear. Here we found that the mRNA expression of JNK3 was continuously high in S1‐treated human ovarian cancer SKOV3/DDP cells using a human unfolded protein response (UPR) pathway PCR array. Pharmacological inhibition of JNK3 increased cell sensitivity to apoptosis induced by S1. Furthermore, inhibition of JNK3 induced accumulation of both acidic compartment and p62, and upregulated ROS production. Our results suggest that JNK3 plays a pro‐survival role during ER stress through preventing the block of autophagic flux and reducing oxidative stress in SKOV3/DDP cells. Inhibition of JNK3 may be a potential method to enhance the killing effect of the Bcl‐2 inhibitor S1. Anat Rec, 298:386–395, 2015. © 2014 Wiley Periodicals, Inc.