xyloketal-b and Glioblastoma

In recent decades, technological advantages have allowed scientists to isolate medicinal compounds from marine organisms that exhibit unique structure and bioactivity. The mangrove fungus Xylaria sp. from the South China Sea is rich in metabolites and produces a potent therapeutic compound, xyloketal B. Since its isolation in 2001, xyloketal B has been extensively studied in a wide variety of cell types and in vitro and in vivo disease models. Xyloketal B and its derivatives exhibit cytoprotective effects in cardiovascular and neurodegenerative diseases by reducing oxidative stress, regulating the apoptosis pathway, maintaining ionic balance, mitigating inflammatory responses, and preventing protein aggregation. Xyloketal B has also shown to alleviate lipid accumulation in a non-alcoholic fatty liver disease model. Moreover, xyloketal B treatment induces glioblastoma cell death. This review summarizes our current understanding of xyloketal B in various disease models.

Topics: Cell Death; Glioblastoma; Humans; Oxidative Stress; Pyrans

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.

Topics: Antineoplastic Agents; Aquatic Organisms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; China; Down-Regulation; Glioblastoma; Humans; MAP Kinase Signaling System; Membrane Potentials; Neoplasm Proteins; Nerve Tissue Proteins; Neurons; Pacific Ocean; Phosphatidylinositol 3-Kinase; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Pyrans; Signal Transduction; TRPM Cation Channels; Wetlands; Xylariales