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

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Journal of Biomedical Science

, 21:61

First Online: 05 July 2014Received: 25 March 2014Accepted: 25 June 2014DOI: 10.1186-1423-0127-21-61

Cite this article as: Tseng, TH., Shen, CH., Huang, WS. et al. J Biomed Sci 2014 21: 61. doi:10.1186-1423-0127-21-61


BackgroundCaffeic 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.

ResultsC6 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.

ConclusionsTaken 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.

KeywordsCaffeic acid phenethyl ester C6 glioma cells Neutral sphingomyelinase p75 neurotrophin receptor MAPK Nerve growth factor Electronic supplementary materialThe online version of this article doi:10.1186-1423-0127-21-61 contains supplementary material, which is available to authorized users.

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Autor: Tsui-Hwa Tseng - Chien-Heng Shen - Wen-Shih Huang - Cheng-Nan Chen - Wen-Hai Liang - Tseng-Hsi Lin - Hsing-Chun Kuo


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