Trichodermin exhibits potent anti-glioblastoma activity by inducing cell cycle arrest and apoptosis, suppressing invasion, and enhancing temozolomide efficacy.

چکیده اصلی

Trichodermin, a sesquiterpene antibiotic from Trichoderma species, shows anticancer potential. In this study, anti-glioblastoma activity was evaluated by (3-(4,5-di methyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay, colony formation, lactate dehydrogenase (LDH) release assay, flow cytometry, wound-healing, transwell invasion, adhesion, Western blot, combination-index analysis, and an orthotopic luciferase glioblastoma mouse model. Trichodermin reduced viability and clonogenicity and increased LDH release of T98G and A172 cells. Trichodermin induced G2/M arrest with p53 activation and downregulation of cyclin B, cyclin A, and cyclin-dependent kinase 1 (CDK1). In addition, trichodermin induced caspase-dependent apoptosis. Invasion, wound healing, and adhesion were suppressed with modulation of epithelial-mesenchymal transition (EMT)-related proteins. Combination index analysis demonstrated a synergistic interaction between trichodermin and temozolomide, possibly due to increased apoptosis. In the mouse model, intraperitoneal trichodermin inhibited intracranial tumour growth and prolonged survival, and increased cleaved caspase-3 expression in tumour tissues. These findings indicate that trichodermin exerts anti-glioblastoma activity and warrants further preclinical evaluation as a potential adjunct to temozolomide therapy.

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