Disclosure of Potential Therapeutic Targets in Plumbagin for Treating Osteosarcoma.

Abstract

Osteosarcoma is one of most malignant bone tumors in children, characterized by high recurrence and metastasis. Plumbagin refers to a bioactive compound that is isolated the herb plant of from Plumbagozeylanica zeylanica L., and it has been proven with potential anti-tumor benefits, including osteosarcoma. However, its pharmacological mechanism remains unclear comprehensively. Thus, this study aimed to reveal potential targets and molecular mechanisms in plumbagin for treating osteosarcoma through bioinformatics method and computational validation. In total, respective 379, 2727 and 2166 genes were ascertained as target genes of plumbagin, osteosarcoma and autophagy. A total of 40 shared genes were identified among plumbagin, osteosarcoma and autophagy. Further, additional 10 core genes were identified and used for enrichment analysis. The findings highlighted the regulatory actions of plumbagin on protein-binding, regulation of autophagy for playing anti-osteosarcoma role. Enriched pathway analysis findings disclosed main molecular pathways, including microRNAs in cancer signaling pathway, Notch signaling pathway. Molecular docking data found that the optimal docking affinity and binding energy between plumbagin and scored protein receptors of glycogen synthase kinase 3 beta (GSK3B), histone deacetylase 2 (HDAC2), poly (ADP-ribose) polymerase 1 (PARP1). Our preclinical study investigates the possible therapeutic mechanism of plumbagin against osteosarcoma, indicating that plumbagin exhibited anti-osteosarcoma features via regulation of core target genes associated with autophagy. Current research findings may provide the scientific ideas and evidences for screening bioactive compound against osteosarcoma.