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Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway

TNF-related apoptosis-inducing ligand (TRAIL) is a tumor-selective apoptosis inducer and has been shown to be promising for treating various types of cancers. However, the application of TRAIL is greatly impeded by the resistance of cancer cells to its action. Studies show that overexpression of som...

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Autores principales: Liu, Jia, Ma, Leina, Wu, Ning, Liu, Ge, Zheng, Lanhong, Lin, Xiukun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178493/
https://www.ncbi.nlm.nih.gov/pubmed/25257790
http://dx.doi.org/10.3390/md12095072
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author Liu, Jia
Ma, Leina
Wu, Ning
Liu, Ge
Zheng, Lanhong
Lin, Xiukun
author_facet Liu, Jia
Ma, Leina
Wu, Ning
Liu, Ge
Zheng, Lanhong
Lin, Xiukun
author_sort Liu, Jia
collection PubMed
description TNF-related apoptosis-inducing ligand (TRAIL) is a tumor-selective apoptosis inducer and has been shown to be promising for treating various types of cancers. However, the application of TRAIL is greatly impeded by the resistance of cancer cells to its action. Studies show that overexpression of some critical pro-survival proteins, such as survivin, is responsible for TRAIL resistance. In this study, we found that Aplysin, a brominated compound from marine organisms, was able to restore the sensitivity of cancer cells to TRAIL both in vitro and in vivo. Aplysin was found to enhance the tumor-suppressing capacity of TRAIL on several TRAIL-resistant cancer cell lines. TRAIL-induced apoptosis was also potentiated in A549 and MCF7 cells treated with Aplysin. Survivin downregulation was identified as a mechanism by which Aplysin-mediated TRAIL sensitization of cancer cells. Furthermore, the activation of p38 MAPK was revealed in Aplysin-treated cancer cells, and its inhibitor SB203580 was able to abrogate the promoting effect of Aplysin on the response of cancer cells to TRAIL action, as evidenced by restored survivin expression, elevated cell survival and reduced apoptotic rates. In conclusion, we provided evidence that Aplysin acts as a sensitizer for TRAIL and its effect on p38 MAPK/survivin pathway may partially account for this activity. Considering its low cytotoxicity to normal cells, Aplysin may be a promising agent for cancer treatment in combination with TRAIL.
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spelling pubmed-41784932014-10-02 Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway Liu, Jia Ma, Leina Wu, Ning Liu, Ge Zheng, Lanhong Lin, Xiukun Mar Drugs Article TNF-related apoptosis-inducing ligand (TRAIL) is a tumor-selective apoptosis inducer and has been shown to be promising for treating various types of cancers. However, the application of TRAIL is greatly impeded by the resistance of cancer cells to its action. Studies show that overexpression of some critical pro-survival proteins, such as survivin, is responsible for TRAIL resistance. In this study, we found that Aplysin, a brominated compound from marine organisms, was able to restore the sensitivity of cancer cells to TRAIL both in vitro and in vivo. Aplysin was found to enhance the tumor-suppressing capacity of TRAIL on several TRAIL-resistant cancer cell lines. TRAIL-induced apoptosis was also potentiated in A549 and MCF7 cells treated with Aplysin. Survivin downregulation was identified as a mechanism by which Aplysin-mediated TRAIL sensitization of cancer cells. Furthermore, the activation of p38 MAPK was revealed in Aplysin-treated cancer cells, and its inhibitor SB203580 was able to abrogate the promoting effect of Aplysin on the response of cancer cells to TRAIL action, as evidenced by restored survivin expression, elevated cell survival and reduced apoptotic rates. In conclusion, we provided evidence that Aplysin acts as a sensitizer for TRAIL and its effect on p38 MAPK/survivin pathway may partially account for this activity. Considering its low cytotoxicity to normal cells, Aplysin may be a promising agent for cancer treatment in combination with TRAIL. MDPI 2014-09-25 /pmc/articles/PMC4178493/ /pubmed/25257790 http://dx.doi.org/10.3390/md12095072 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Liu, Jia
Ma, Leina
Wu, Ning
Liu, Ge
Zheng, Lanhong
Lin, Xiukun
Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway
title Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway
title_full Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway
title_fullStr Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway
title_full_unstemmed Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway
title_short Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway
title_sort aplysin sensitizes cancer cells to trail by suppressing p38 mapk/survivin pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178493/
https://www.ncbi.nlm.nih.gov/pubmed/25257790
http://dx.doi.org/10.3390/md12095072
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