Identification of a Natural Small Molecule Dauricine for Glioma Therapy through Targeting p53 and VEGFA Pathways

Glioma is a highly malignant primary brain tumor with a poor prognosis. Current treatments for intracranial glioma are often ineffective, necessitating the development of novel therapeutic agents. In this work, molecular docking-based screening analyses were conducted to identify dauricine as a dual-targeted agent of p53 and VEGFA by targeting the Loop1/Sheet3 (L1/S3) pocket of p53 and the Loop1/Loop3 (L1/L3) regions of VEGFA. The anticancer activity of dauricine was further evaluated using MTT, colony formation, wound-healing, transwell invasion, Western blot, and apoptosis assays, including Hoechst staining and flow cytometry on U87 and C6 glioma cell lines. A C6 xenograft model in BALB/c-nu mice was used to assess tumor growth inhibition. The in vivo anticancer effect of dauricine was detected by HE staining, and the levels of p53 and VEGFA were tested by IHC staining. The results showed that dauricine significantly inhibited the proliferation, migration, and invasion of glioma cells, induced apoptosis, and reduced tumor growth both in vitro and in vivo. Western blot analyses showed that dauricine upregulated p53 and downregulated VEGFA pathways. In vivo experiments demonstrated that dauricine inhibited the growth of subcutaneous tumors in nude mice by targeting p53 and VEGFA. Overall, these results demonstrated that dauricine suppresses glioma growth by targeting the p53 and VEGFA pathways, making it a promising anticancer agent for glioma treatment.