Network Pharmacology and Bioinformatics Analysis to Identify the Molecular Targets and its Biological Mechanisms of Sciadopitysin against Glioblastoma

TL;DR

This study uses network pharmacology to identify how sciadopitysin may treat glioblastoma by targeting HSP90 and AKT1 proteins.

Contribution

The study introduces a network pharmacology approach to uncover sciadopitysin's molecular targets and mechanisms in glioblastoma.

Findings

Sixty-four potential targets of sciadopitysin against glioblastoma were identified.

HSP90 and AKT1 were found to be key hub genes in the protein interaction network.

Sciadopitysin showed cytotoxic effects on GBM U87 cells in vitro.

Abstract

Glioblastoma multiform (GBM) is categorized as the most malignant subtype of gliomas, which comprise nearly 75% of malignant brain tumors in adults. Increasing evidence suggests that network pharmacology will be a novel method for identifying the systemic mechanism of therapeutic compounds in diseases like cancer. The present study aimed to use a network pharmacology approach to establish the predictive targets of sciadopitysin against GBM and elucidate its biological mechanisms. Firstly, targets of sciadopitysin were obtained from the SwissTargetPrediction database, and genes associated with the pathogenesis of GBM were identified from the DiGeNET database. Sixty-four correlative hits were identified as anti-glioblastoma targets of sciadopitysin. Functional enrichment and pathway analysis revealed significant biological mechanisms of the targets. Interaction of protein network and cluster analysis using STRING resulted in two crucial interacting hub genes, namely, HSP90 and AKT1. Additionally, the in vitro cytotoxic potential of sciadopitysin was assessed on GBM U87 cells. The findings indicate that the pharmacological action of sciadopitysin against GBM might be associated with the regulation of two core targets: HSP90 and AKT1. Thus, the network pharmacology undertaken in the current study established the core active targets of sciadopitysin, which may be extensively applied with further validations for treatment in GBM.

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