Farnesylthiosalicylic acid induces caspase activation and apoptosis in glioblastoma cells

S Amos, G T Redpath, G Polar, R McPheson, D Schiff, I M Hussaini
2005 Cell Death and 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 3 Hthymidine 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
more » ... 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 EGFinduced 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.
doi:10.1038/sj.cdd.4401783 pmid:16239932 fatcat:w3tqpy2nnndr7iyoh3gq7avyom