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• W2588891882 abstract "// Jihyun Lee 1, * , Eun Jung Sohn 1, * , Sangwook Yoon 1 , Gunho Won 1 , Chang Geun Kim 1 , Ji Hoon Jung 1 , Sung-Hoon Kim 1 1 College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, 130-701, Republic of Korea * These authors have contributed equally to this work Correspondence to: Sung-Hoon Kim, email: sungkim7@khu.ac.kr Keywords: tanshinone I, autophagy, p62 ΔUBA , IRE1, mesothelioma cells Received: October 27, 2016      Accepted: January 16, 2017      Published: February 15, 2017 ABSTRACT The aim of present study is to elucidate autophagic mechanism of tanshinone I (Tan I) in H28 and H2452 mesothelioma cells. Herein, Tan I exerted cytotoxicity with autophagic features of autophagy protein 5 (ATG5)/ microtubule-associated protein 1A/1B-light chain 3II (LC3 II) activation, p62/sequestosome 1 (SQSTM1) accumulation and increased number of LC3II punctae, acridine orange-stained cells and autophagic vacuoles. However, 3-methyladenine (3MA) and NH 4 Cl increased cytotoxicity in Tan I treated H28 cells. Furthermore, autophagy flux was enhanced in Tan I-treated H28 cells transfected by RFP-GFP-LC3 constructs, with colocalization of GFP-LC3 punctae with LAMP1 or Lysotracker. Interestingly, C-terminal UBA domain is required for Tan 1 induced aggregation of p62 in H28 cells. Notably, Tan I upregulated CCAAT-enhancer-binding protein homologous protein (CHOP), inositol-requiring protein-1 (IRE1) and p-c-Jun N-terminal kinase (p-JNK), but silencing of IRE1 or p62 and JNK inhibitor SP600125 blocked the LC3II accumulation in Tan I-treated H28 cells. Overall, these findings demonstrate that Tan I exerts antitumor activity through a compromise between apoptosis and p62/SQSTM1-dependent autophagy via activation of JNK and IRE 1 in malignant mesothelioma cells." @default.
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• W2588891882 date "2017-02-15" @default.
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• W2588891882 title "Activation of JNK and IRE1 is critically involved in tanshinone I-induced p62 dependent autophagy in malignant pleural mesothelioma cells: implication of p62 UBA domain" @default.
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• W2588891882 doi "https://doi.org/10.18632/oncotarget.15336" @default.
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