Schweinfurthin A Selectively Inhibits Proliferation and Rho Signaling in Glioma and Neurofibromatosis Type 1 Tumor Cells in a NF1-GRD–Dependent Manner

摘要: Neurofibromatosis type 1 (NF1) is the most common genetic disease affecting nervous system. Patients typically develop many tumors over their lifetime, leading to increased morbidity and mortality. The NF1 gene, mutated in NF1, also commonly sporadic glioblastoma multiforme (GBM). Because both GBM are currently incurable, new therapeutic approaches clearly needed. Natural products represent an opportunity therapies, as they have been evolutionarily selected play targeted roles organisms. Schweinfurthin A a prenylated stilbene natural product that has previously shown specific inhibitory activity against brain hematopoietic tumor lines. We show patient-derived malignant peripheral nerve sheath (MPNST) lines, well lines derived from Nf1-/+;Trp53-/+ (NPcis) mouse model of astrocytoma MPNST highly sensitive inhibition by schweinfurthin its synthetic analogs. In contrast, primary astrocytes resistant growth effects A, suggesting may act specifically on cells. Stable transfection GTPase-activating protein related domain Nf1 into Nf1-/-;Trp53-/- cells confers resistance A. addition, profound effect dynamic reorganization actin cytoskeleton led us discover inhibits factor-stimulated Rho signaling. summary, we identified class small molecules inhibit central system seem NF1-deficient through cytoskeletal correlating changes