In silico studies reveal the anti-osteosarcoma targets and action mechanisms of resveratrol

Abstract

Previous reports have discovered the anticancer activity of resveratrol in preclinical experiments, especially towards osteosarcoma (OS). However, the comprehensive anti-OS mechanisms of resveratrol remain unexplored. First, we used computational bioinformatics, such as network pharmacology and molecular docking, to identify the putative biotargets and mechanisms of resveratrol against OS. Second, the crucial biotargets identified were validated using cultured samples. All resveratrol and OS-related genes, and overlapping genes were obtained. Enrichment analysis revealed in-depth molecular mechanisms of resveratrol against OS. Other core targets of resveratrol against OS were identified accordingly. The identified core targets of tumor protein p53 (TP53), E1A-binding protein p300 (EP300), sarcoma gene (SRC) were then validated in vitro. We observed that resveratrol-administered OS cells exhibited suppressed cell proliferation, increased TP53 protein activation, and decreased cellular EP300 and SRC protein expression levels. Collectively, we report that resveratrol action may regulate multiple targets to exert anti-OS pharmacological responses and may serve as a promising bioactive compound for the clinical treatment of OS.