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Mar. Drugs 2015, 13(4), 2505-2525; doi:10.3390/md13042505

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

1
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
2
Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
3
Department of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
4
Faculty of Applied Science & Engineering, University of Toronto, Toronto, ON M5S 1A4, Canada
5
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
6
Key Laboratory of Functional Molecules from Oceanic Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, Guangzhou 510080, China
7
Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
*
Author to whom correspondence should be addressed.
Academic Editors: Sergey A. Dyshlovoy and Friedemann Honecker
Received: 30 January 2015 / Revised: 3 April 2015 / Accepted: 8 April 2015 / Published: 22 April 2015
(This article belongs to the Collection Marine Compounds and Cancer)
View Full-Text   |   Download PDF [1337 KB, uploaded 22 April 2015]   |  

Abstract

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. View Full-Text
Keywords: glioblastoma; xyloketal B; proliferation; migration; TRPM7; marine compound glioblastoma; xyloketal B; proliferation; migration; TRPM7; marine compound
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Chen, W.-L.; Turlova, E.; Sun, C.L.F.; Kim, J.-S.; Huang, S.; Zhong, X.; Guan, Y.-Y.; Wang, G.-L.; Rutka, J.T.; Feng, Z.-P.; Sun, H.-S. Xyloketal B Suppresses Glioblastoma Cell Proliferation and Migration in Vitro through Inhibiting TRPM7-Regulated PI3K/Akt and MEK/ERK Signaling Pathways. Mar. Drugs 2015, 13, 2505-2525.

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