Farnesylthiosalicylic Acid Induces Caspase Activation and Apoptosis in Glioblastoma Cells
Cell Death & Differentiation
Primary glioblastomas (GBMs) commonly overexpress the oncogene epidermal growth factor receptor (EGFR), which leads to increased Ras activity. FTA, a novel Ras inhibitor, produced both time- and dose-dependent caspase-mediated apoptosis in GBM cell lines. EGFR-mediated increase in 3H-thymidine uptake was inhibited by FTA. FACS analysis was performed to determine the percent of apoptotic cells. The sub-Go population of GBM cells was increased from 4.5 to 13.8% (control) to over 45–53.6% in FTA-treated cells within 24 h. Furthermore, FTA also increased the activities of both caspase-3 and -9, and PARP cleavage. Treatment of GBMs with FTA before or after EGF addition to the cultures blocked phosphorylation of Akt and mitogen-activated protein kinases (MAPK). FTA also significantly reduced the amount of EGF-induced Ras-GTP as reflected by a decrease in the level of Ras bound to Raf-RBD-GST. This study demonstrates that inhibition of Ras methylation may provide a therapeutic target for the treatment of GBMs overexpressing EGFR.
Glioblastoma, farnesylthiosalicylic acid, apoptosis, epidermal growth factor receptor, Ras, caspase
Amos, Samson; Redpath, G. T.; Polar, G.; McPheson, R.; Schiff, D.; and Hussaini, I. M., "Farnesylthiosalicylic Acid Induces Caspase Activation and Apoptosis in Glioblastoma Cells" (2006). Pharmaceutical Sciences Faculty Publications. 110.