Apr 20, 2020

A Systems Pharmacology Approach based on Oncogenic Signalling Pathways to Determine the Mechanisms of Action of Natural Products in Breast Cancer from Transcriptome Data

BioRxiv : the Preprint Server for Biology
R. OdongoTunahan Cakir

Abstract

Background: Plant-derived natural products possess poly-pharmacologic mechanisms of action with good tolerability and thus are appropriate in the management of complex diseases, especially cancers. However, methodological limitations impede attempts to catalogue targeted processes and infer systemic mechanisms of action. Integrative systems biology approaches are better suited in these cases due to their analytical comprehensiveness. Method: The transcriptome data from drug-treated breast cancer cell lines were mapped on human protein interactome to construct targeted subnetworks. The subnetworks were analysed in terms of enriched oncogenic signalling pathways by reducing redundancy through pathway-pathway interaction networks, and the filtered pathways were mapped on oncogenesis processes. Results: The signalling pathways regulated by the pleiotropic effects of Actein, Withaferin A, Indole-3-Carbinol and Compound Kushen were found to be projected on a set of oncogenesis processes at the transcriptomic level in different breast cancer subtypes (triple negative, luminal A and HER2+). Notably, these compounds indirectly regulated known oncogenes in the different subtypes through their associated pathways in the subnetworks. Concl...Continue Reading

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Mentioned in this Paper

Disease Transmission
Aedes aegypti
Arboviruses
Aedes
Aedes albopictus
Zika Virus Disease (Disorder)
Disseminated
Asians
Chikungunya virus
Flavivirus

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