Network-Guided Identification of Plant-Derived Modulators of Stress-Adaptive Signalling in Neuroblastoma
Abstract
Neuroblastoma is characterized by noticeable resistance to chemotherapy, largely driven by the ability of tumour cells to reorganize stress-adaptive signalling networks rather than relying on single oncogenic drivers. We conducted a study to investigate the pharmacological mode of action of doxorubicin in modifying adaptive signalling pathways in SH-SY5Y neuroblastoma cells, and whether the capacity of plant metabolites can exploit emergent biochemical vulnerabilities. Transcriptomic profiling through RNA sequencing conducted 48 h post-doxorubicin exposure unveiled the organized disruption of pathways linked with amyloidogenic processes, oncogenic signalling pathways, oxidative stress, and DNA repair. The protein-protein interactions, coupled with Kyoto Encyclopedia of Genes and Genomes pathway evaluations, revealed five network-central-hubs: BRAF, GSK3β, PARP1, BACE1, and MAOB. Structural docking integrated with 200 ns molecular dynamics simulations illustrated binding stability across multiple targets driven by three metabolites, Lactol binding to BRAF (-54.13 kcal/mol) and MAOB (-39.08 kcal/mol), Amino(1H-indol-2-yl)acetic acid to BACE1 (-41.07 kcal/mol) and GSK3β (-47.38 kcal/mol), and Quercetin-3-(6″-malonyl-glucoside) binding to PARP1 (-46.03 kcal/mol). In vitro Cell Counting Kit-8 proliferation assays validated the significant anti-neuroblastoma efficacy, with the lowest IC50 (0.2397 µM) being exhibited by Amino(1H-indol-2-yl)acetic acid, followed by Lactol (1.226 µM)…
Read the paper
Related studies
- Quercetin Influences Quorum Sensing in Food Borne Bacteria: In-Vitro and In-Silico Evidence
- Phenolic-protein interactions: insight from in-silico analyses – a review
- In Silico Discovery of Candidate Drugs against Covid-19
- Neuropharmacological Effects of Quercetin: A Literature-Based Review
- In vitro and in silico anti-dengue activity of compounds obtained from Psidium guajava through bioprospecting
- Effect of Quercetin Rich Onion Extracts on Bacterial Quorum Sensing
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.