Abstract
Glioblastoma multiforme (GBM) is the most common form of malignant brain tumor, with poor prognosis; the efficacy of current standard therapy for GBM remains unsatisfactory. Magnolol, an herbal medicine from Magnolia officinalis, exhibited anticancer properties against many types of cancers. However, whether magnolol suppresses GBM progression as well as its underlying mechanism awaits further investigation. In this study, we used the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay, apoptosis marker analysis, transwell invasion and wound-healing assays to identify the effects of magnolol on GBM cells. We also validated the potential targets of magnolol on GBM with the GEPIA (Gene Expression Profiling Interactive Analysis) and Western blotting assay. Magnolol was found to trigger cytotoxicity and activate extrinsic/intrinsic apoptosis pathways in GBM cells. Both caspase-8 and caspase-9 were activated by magnolol. In addition, GEPIA data indicated the PKCδ (Protein kinase C delta)/STAT3 (Signal transducer and activator of transcription 3) signaling pathway as a potential target of GBM. Magnolol effectively suppressed the phosphorylation and nuclear translocation of STAT3 in GBM cells. Meanwhile, tumor invasion and migration ability and the associated genes, including MMP-9 (Matrix metalloproteinase-9) and uPA (Urokinase-type plasminogen activator), were all diminished by treatment with magnolol. Taken together, our results suggest that magnolol-induced anti-GBM effect may be associated with the inactivation of PKCδ/STAT3 signaling transduction.
Highlights
The main purpose of the present study was to verify whether initiation of extrinsic/intrinsic pathways and suppression of STAT3 signaling are associated with magnolol-induced apoptosis and invasion inhibition on Glioblastoma multiforme (GBM) cells
We further investigated whether magnolol may induce apoptosis of GBM8401 cells
These results indicated that PKCδ/STAT3 signaling pathway may be an important target for GBM treatment
Summary
Development of effective anti-GBM agents with less toxicity is crucial for improving survival of patients. Herbal medicines have been recognized as potential complementary strategies for GBM [3]. Trogrlic et al presented that a phytotherapy involving five types of herbal medicines was conducive to therapeutic and survival benefits of standard oncological treatment for GBM [4]. Medicinal herbs were demonstrated to induce GBM regression in cell and animal models. It was found that bioactive compounds isolated from medicinal herbs mediate anticancer activities, such as cell cycle inhibition, antitumor immune responses, suppression of oncogenic signal pathways, autophagy and apoptosis [3,5,6,7]
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