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Xyloketal B Suppresses Glioblastoma Cell Proliferation and Migration in Vitro through Inhibiting TRPM7-Regulated PI3K/Akt and MEK/ERK Signaling Pathways

Glioblastoma, the most common and aggressive type of brain tumors, has devastatingly proliferative and invasive characteristics. The need for finding a novel and specific drug target is urgent as the current approaches have limited therapeutic effects in treating glioblastoma. Xyloketal B is a marin...

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Autores principales: Chen, Wen-Liang, Turlova, Ekaterina, Sun, Christopher L. F., Kim, Ji-Sun, Huang, Sammen, Zhong, Xiao, Guan, Yong-Yuan, Wang, Guan-Lei, Rutka, James T., Feng, Zhong-Ping, Sun, Hong-Shuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413223/
https://www.ncbi.nlm.nih.gov/pubmed/25913706
http://dx.doi.org/10.3390/md13042505
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author Chen, Wen-Liang
Turlova, Ekaterina
Sun, Christopher L. F.
Kim, Ji-Sun
Huang, Sammen
Zhong, Xiao
Guan, Yong-Yuan
Wang, Guan-Lei
Rutka, James T.
Feng, Zhong-Ping
Sun, Hong-Shuo
author_facet Chen, Wen-Liang
Turlova, Ekaterina
Sun, Christopher L. F.
Kim, Ji-Sun
Huang, Sammen
Zhong, Xiao
Guan, Yong-Yuan
Wang, Guan-Lei
Rutka, James T.
Feng, Zhong-Ping
Sun, Hong-Shuo
author_sort Chen, Wen-Liang
collection PubMed
description Glioblastoma, the most common and aggressive type of brain tumors, has devastatingly proliferative and invasive characteristics. The need for finding a novel and specific drug target is urgent as the current approaches have limited therapeutic effects in treating glioblastoma. Xyloketal B is a marine compound obtained from mangrove fungus Xylaria sp. (No. 2508) from the South China Sea, and has displayed antioxidant activity and protective effects on endothelial and neuronal oxidative injuries. In this study, we used a glioblastoma U251 cell line to (1) explore the effects of xyloketal B on cell viability, proliferation, and migration; and (2) investigate the underlying molecular mechanisms and signaling pathways. MTT assay, colony formation, wound healing, western blot, and patch clamp techniques were employed. We found that xyloketal B reduced cell viability, proliferation, and migration of U251 cells. In addition, xyloketal B decreased p-Akt and p-ERK1/2 protein expressions. Furthermore, xyloketal B blocked TRPM7 currents in HEK-293 cells overexpressing TRPM7. These effects were confirmed by using a TRPM7 inhibitor, carvacrol, in a parallel experiment. Our findings indicate that TRPM7-regulated PI3K/Akt and MEK/ERK signaling is involved in anti-proliferation and migration effects of xyloketal B on U251 cells, providing in vitro evidence for the marine compound xyloketal B to be a potential drug for treating glioblastoma.
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spelling pubmed-44132232015-05-07 Xyloketal B Suppresses Glioblastoma Cell Proliferation and Migration in Vitro through Inhibiting TRPM7-Regulated PI3K/Akt and MEK/ERK Signaling Pathways Chen, Wen-Liang Turlova, Ekaterina Sun, Christopher L. F. Kim, Ji-Sun Huang, Sammen Zhong, Xiao Guan, Yong-Yuan Wang, Guan-Lei Rutka, James T. Feng, Zhong-Ping Sun, Hong-Shuo Mar Drugs Article Glioblastoma, the most common and aggressive type of brain tumors, has devastatingly proliferative and invasive characteristics. The need for finding a novel and specific drug target is urgent as the current approaches have limited therapeutic effects in treating glioblastoma. Xyloketal B is a marine compound obtained from mangrove fungus Xylaria sp. (No. 2508) from the South China Sea, and has displayed antioxidant activity and protective effects on endothelial and neuronal oxidative injuries. In this study, we used a glioblastoma U251 cell line to (1) explore the effects of xyloketal B on cell viability, proliferation, and migration; and (2) investigate the underlying molecular mechanisms and signaling pathways. MTT assay, colony formation, wound healing, western blot, and patch clamp techniques were employed. We found that xyloketal B reduced cell viability, proliferation, and migration of U251 cells. In addition, xyloketal B decreased p-Akt and p-ERK1/2 protein expressions. Furthermore, xyloketal B blocked TRPM7 currents in HEK-293 cells overexpressing TRPM7. These effects were confirmed by using a TRPM7 inhibitor, carvacrol, in a parallel experiment. Our findings indicate that TRPM7-regulated PI3K/Akt and MEK/ERK signaling is involved in anti-proliferation and migration effects of xyloketal B on U251 cells, providing in vitro evidence for the marine compound xyloketal B to be a potential drug for treating glioblastoma. MDPI 2015-04-22 /pmc/articles/PMC4413223/ /pubmed/25913706 http://dx.doi.org/10.3390/md13042505 Text en © 2015 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/4.0/).
spellingShingle Article
Chen, Wen-Liang
Turlova, Ekaterina
Sun, Christopher L. F.
Kim, Ji-Sun
Huang, Sammen
Zhong, Xiao
Guan, Yong-Yuan
Wang, Guan-Lei
Rutka, James T.
Feng, Zhong-Ping
Sun, Hong-Shuo
Xyloketal B Suppresses Glioblastoma Cell Proliferation and Migration in Vitro through Inhibiting TRPM7-Regulated PI3K/Akt and MEK/ERK Signaling Pathways
title Xyloketal B Suppresses Glioblastoma Cell Proliferation and Migration in Vitro through Inhibiting TRPM7-Regulated PI3K/Akt and MEK/ERK Signaling Pathways
title_full Xyloketal B Suppresses Glioblastoma Cell Proliferation and Migration in Vitro through Inhibiting TRPM7-Regulated PI3K/Akt and MEK/ERK Signaling Pathways
title_fullStr Xyloketal B Suppresses Glioblastoma Cell Proliferation and Migration in Vitro through Inhibiting TRPM7-Regulated PI3K/Akt and MEK/ERK Signaling Pathways
title_full_unstemmed Xyloketal B Suppresses Glioblastoma Cell Proliferation and Migration in Vitro through Inhibiting TRPM7-Regulated PI3K/Akt and MEK/ERK Signaling Pathways
title_short Xyloketal B Suppresses Glioblastoma Cell Proliferation and Migration in Vitro through Inhibiting TRPM7-Regulated PI3K/Akt and MEK/ERK Signaling Pathways
title_sort xyloketal b suppresses glioblastoma cell proliferation and migration in vitro through inhibiting trpm7-regulated pi3k/akt and mek/erk signaling pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413223/
https://www.ncbi.nlm.nih.gov/pubmed/25913706
http://dx.doi.org/10.3390/md13042505
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