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

Marine Drugs

Wen-Liang Chen¹  Ekaterina Turlova¹  Christopher L. F. Sun³  Ji-Sun Kim¹  Sammen Huang¹  Xiao Zhong¹  Yong-Yuan Guan²  Guan-Lei Wang²  James T. Rutka⁵  Zhong-Ping Feng¹  Hong-Shuo Sun¹  Sergey A. Dyshlovoy⁴ 

[1] Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; E-Mails:;Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; E-Mails:;Faculty of Applied Science & Engineering, University of Toronto, Toronto, ON M5S 1A4, Canada; E-Mail:Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada;;Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; E-Mail:

关键词: glioblastoma;    xyloketal B;    proliferation;    migration;    TRPM7;    marine compound;   

DOI  :  10.3390/md13042505

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.