Nerolidol inhibited U-251 human glioblastoma cell proliferation and triggered apoptosis via the upregulation of the p38 MAPK signaling pathway.

Abstract

Glioblastoma multiforme (GBM) is a lethal brain tumor with high mortality and morbidity. Nerolidol (NRD) is a sesquiterpene alcohol sequestered from the essential oils of aromatic florae with potent antioxidant, antiviral, anticancer, cardioprotective, and neuroprotective activity. The aim of the study was to investigate the underlying cell-cycle mechanisms of NRD-mediated antiproliferative and apoptosis activities in GBM using human U-251 cells. The current research investigated the antiproliferative and apoptotic activities of NRD on U-251 cells. The effects of NRD were measured using a Cell Counting Kit-8 (CCK-8) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, messenger ribonucleic acid (mRNA) level assessment, and western blot assay. Nerolidol decreased U-251 viability in a dose-dependent manner, as well as induced apoptotic activity, reduced B-cell lymphoma-2 (BCL-2) levels, and increased mRNA expression of BCL-2-associated X (Bax), caspase-3 and caspase-9. The attenuation of the cyclin-D1, cyclin-dependent kinase 4 (CDK4) and CDK6 mRNA expression confirmed cell cycle regulation. Western blot analysis of CDK1 indicated reductions in cyclin-B1 and p21. Furthermore, NRD prompted apoptosis through p38 amelioration and increased phosphorylated extracellular signal-related kinase 1 (p-ERK1) and phosphorylated c-Jun N-terminal protein kinase 1 (p-JNK1) levels. Nerolidol inhibited GBM cell viability and induced apoptosis through the regulation of cell-cycle proteins via p38 mitogen-activated protein kinase (MAPK) signaling pathways. Thus, NRD could be developed as a potential natural therapeutic agent for GBM.