Activation of neutral-sphingomyelinase, MAPKs, and p75 NTR-mediating caffeic acid phenethyl ester–induced apoptosis in C6 glioma cells

Journal of Biomedical Science

Hsing-Chun Kuo¹  Tseng-Hsi Lin⁵  Wen-Hai Liang⁴  Cheng-Nan Chen⁶  Wen-Shih Huang⁷  Chien-Heng Shen²  Tsui-Hwa Tseng³ 

[1] Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan;Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Department of Medical Education, Chung Shan Medical University Hospital, No. 110, Section 1, Chien-Kuo N. Road, Taichung 402, Taiwan;Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan;Department of Internal Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan;Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan;Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan

关键词: Nerve growth factor;    MAPK;    p75 neurotrophin receptor;    Neutral sphingomyelinase;    C6 glioma cells;    Caffeic acid phenethyl ester;   

Others  :  1137628
DOI  :  10.1186/1423-0127-21-61

 received in 2014-03-25, accepted in 2014-06-25,  发布年份 2014

【 摘 要 】

Background

Caffeic acid phenethyl ester (CAPE), a component of propolis, is reported to possess anti-inflammatory, anti-bacterial, anti-viral, and anti-tumor activities. Previously, our laboratory demonstrated the in vitro and in vivo bioactivity of CAPE and addressed the role of p53 and the p38 mitogen-activated protein kinase (MAPK) pathway in regulating CAPE-induced apoptosis in C6 glioma cells.

Results

C6 cancer cell lines were exposed to doses of CAPE; DNA fragmentation and MAPKs and NGF/P75NTR levels were then determined. SMase activity and ceramide content measurement as well as western blotting analyses were performed to clarify molecular changes. The present study showed that CAPE activated neutral sphingomyelinase (N-SMase), which led to the ceramide-mediated activation of MAPKs, including extracellular signal-regulated kinase (ERK), Jun N-terminus kinase (JNK), and p38 MAPK. In addition, CAPE increased the expression of nerve growth factor (NGF) and p75 neurotrophin receptor (p75NTR). The addition of an N-SMase inhibitor, GW4869, established that NGF/p75NTR was the downstream target of N-SMase/ceramide. Pretreatment with MAPK inhibitors demonstrated that MEK/ERK and JNK acted upstream and downstream, respectively, of NGF/p75NTR. Additionally, CAPE-induced caspase 3 activation and poly [ADP-ribose] polymerase cleavage were reduced by pretreatment with MAPK inhibitors, a p75NTR peptide antagonist, or GW4869.

Conclusions

Taken together, N-SMase activation played a pivotal role in CAPE-induced apoptosis by activation of the p38 MAPK pathway and NGF/p75NTR may explain a new role of CAPE induced apoptosis in C6 glioma.

【 授权许可】

   
2014 Tseng et al.; licensee BioMed Central Ltd.

【 图 表 】

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