Tanshinone IIA induces TRAIL sensitization of glioblastoma through death receptors induction and STAT3 pathway inhibition

2021 ◽  
pp. 147515
Author(s):  
Xiaokun Zhou ◽  
Liang Lv ◽  
Yuan Tan ◽  
Zhongyi Zhang ◽  
Shuyang Wei ◽  
...  
2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 334-334
Author(s):  
Zhi-wen Song ◽  
Cheng-long Jin ◽  
Mao Ye ◽  
Chun-qi Gao ◽  
Hui-chao Yan ◽  
...  

Abstract Apoptosis is programmed cell death that can be stimulated by external stress or nutrition restrictions. Lysine (Lys) is an essential amino acid for pig growth, and the relationship between Lys deficiency caused apoptosis and inhibition of skeletal muscle growth remains unknown. The objective of this study was to investigate whether apoptosis could be regulated by Lys supplementation and the potential mechanism. In current work, 30 male Duroc × Landrace × Large weaned piglets were divided randomly into 3 groups: control group (Lys 1.30%), Lys deficiency group (Lys 0.86%), and Lys rescue group (Lys 0.86%, 0-14d; 1.30%,15–28 d). The experiment lasted for 28 days, and on the morning of 29 d, piglets were slaughtered to collect samples. Isobaric tag for relative and absolute quantification (iTRAQ) proteomics analysis of the longissimus dorsi muscle showed that Janus family tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) pathway was involved in Lys deficiency-induced apoptosis and inhibited skeletal muscle growth. Meanwhile, western blotting results of the longissimus dorsi muscle demonstrated that Lys deficiency caused apoptosis (P < 0.05) with the JAK2-STAT3 pathway inhibition (P < 0.05). Interestingly, apoptosis was suppressed (P < 0.05), and the JAK2-STAT3 pathway was reactivated (P < 0.05) after Lys re-supplementation in longissimus dorsi muscle. In addition, results of satellite cells (SCs) isolated from the longissimus dorsi muscle of 5-day-old Landrace piglets showed that Lys deficiency-induced apoptosis (P < 0.05) was mediated by the JAK2-STAT3 pathway inhibition (P < 0.05). Moreover, the JAK2-STAT3 pathway was reactivated (P < 0.05) by Lys re-supplementation and suppressed apoptosis in SCs (P < 0.05), and this effect was blocked (P < 0.05) after SCs treated with AG-490 (a specific inhibitor of JAK2). Collectively, Lys inhibited apoptosis in SCs to govern skeletal muscle growth via the JAK2-STAT3 pathway.


PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e55183 ◽  
Author(s):  
Ly Quoc Trung ◽  
J. Luis Espinoza ◽  
Akiyoshi Takami ◽  
Shinji Nakao

2012 ◽  
Vol 258 (1) ◽  
pp. 72-81 ◽  
Author(s):  
Miran Jo ◽  
Mi Hee Park ◽  
Pushpa Saranya Kollipara ◽  
Byeong Jun An ◽  
Ho Sueb Song ◽  
...  

2019 ◽  
Vol 25 (2) ◽  
pp. 769-775 ◽  
Author(s):  
Jianying Jin ◽  
Qunyi Guo ◽  
Jingjing Xie ◽  
Dan Jin ◽  
Yanan Zhu

2017 ◽  
Vol 40 (8) ◽  
pp. 1306-1313 ◽  
Author(s):  
Wei Lou ◽  
Yan Chen ◽  
Ke-ying Zhu ◽  
Huizi Deng ◽  
Tianhao Wu ◽  
...  

2015 ◽  
Vol 87 (3) ◽  
pp. 543-560 ◽  
Author(s):  
Goldie Y. L. Lui ◽  
Zaklina Kovacevic ◽  
Sharleen V. Menezes ◽  
Danuta S. Kalinowski ◽  
Angelica M. Merlot ◽  
...  

2012 ◽  
Vol 303 (3) ◽  
pp. E410-E421 ◽  
Author(s):  
Andrea Bonetto ◽  
Tufan Aydogdu ◽  
Xiaoling Jin ◽  
Zongxiu Zhang ◽  
Rui Zhan ◽  
...  

Cachexia, the metabolic dysregulation leading to sustained loss of muscle and adipose tissue, is a devastating complication of cancer and other chronic diseases. Interleukin-6 and related cytokines are associated with muscle wasting in clinical and experimental cachexia, although the mechanisms by which they might induce muscle wasting are unknown. One pathway activated strongly by IL-6 family ligands is the JAK/STAT3 pathway, the function of which has not been evaluated in regulation of skeletal muscle mass. Recently, we showed that skeletal muscle STAT3 phosphorylation, nuclear localization, and target gene expression are activated in C26 cancer cachexia, a model with high IL-6 family ligands. Here, we report that STAT3 activation is a common feature of muscle wasting, activated in muscle by IL-6 in vivo and in vitro and by different types of cancer and sterile sepsis. Moreover, STAT3 activation proved both necessary and sufficient for muscle wasting. In C2C12 myotubes and in mouse muscle, mutant constitutively activated STAT3-induced muscle fiber atrophy and exacerbated wasting in cachexia. Conversely, inhibiting STAT3 pharmacologically with JAK or STAT3 inhibitors or genetically with dominant negative STAT3 and short hairpin STAT3 reduced muscle atrophy downstream of IL-6 or cancer. These results indicate that STAT3 is a primary mediator of muscle wasting in cancer cachexia and other conditions of high IL-6 family signaling. Thus STAT3 could represent a novel therapeutic target for the preservation of skeletal muscle in cachexia.


2014 ◽  
Vol 10 (6) ◽  
pp. 2905-2911 ◽  
Author(s):  
MENG ZHANG ◽  
ZHI-GANG BIAN ◽  
YI ZHANG ◽  
JIA-HE WANG ◽  
LIANG KAN ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document