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 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.     

Zinc and Boron Application at Different Phenological Stages Alleviates Tree Growth,Fruit Yield and Quality of Sweet Orange Cv. ‘Blood Red’

The deficiency of micronutrients, particularly zinc (Zn) and boron (B) has affected vegetative growth, yield and fruit quality of sweet orange in many citrus growing areas of Pakistan. The present study was conducted in 2015 and 2016 to determine the impact of Zn and B supplementation on growth and quality of sweet orange cv. ‘Blood red’. Pre-harvest foliar application of variant Zn and B levels was done at different phenological stages of fruit growth and development, i.e., full bloom, fruit set and premature stage. Results have concluded that pre-harvest foliar application of Zn and B augmented phosphorous, Zn, B, potassium, iron, and manganese contents in leaves, particularly Zn and B content from deficient to optimal level. Moreover, the combined application of Zn and B has also significantly enhanced vegetative characters such as tree height and spread along with reproductive characters, i.e., incremented numbers of fruit, fruit weight, total soluble solids, titratable acidity and ascorbic acid contents. However, among stage comparison, outcomes depicted that foliar application of Zn and B at full bloom?+?fruit set?+?premature stage resulted in maximum production with high quality fruits.