Cananga odorata (Ylang-Ylang) modulate pathways involved in cancer: Gene set enrichment and network pharmacology approach

Abstract

Traditionally, Cananga odorata Hook. F. & Thomson (Ylang-Ylang) is commonly used to treat various diseases and has been assessed for anti-cancer potency in experimental animal models. However, the affinity of its phytocompounds with multiple proteins involved in the pathogenesis of cancer has not been illuminated yet. The present study was framed to elucidate the molecular mechanisms of Cananga odorata for its anticancer activity via compound-gene set pathway enrichment analysis, network pharmacology, and docking studies. Initially, phytocompounds were retrieved from herbs databases and literature. Structural information of each compound was obtained from the PubChem database. Druggable characteristics and side effects were predicted using MolSoft and ADVERpred. ADMET profile was predicted using PreADMET online server. Possible target proteins of each compound were predicted by BindingDB (p≥0.7). Compounds modulating the target proteins associated with the cancer were separated based on the successful and approved targets available in the Therapeutic Target Database. STRING and KEGG pathway database was used to analyze the molecular pathways modulated by the protein targets. The interaction between compounds, proteins, and pathways was constructed by Cytoscape 3.6.1, and docking of compounds with protein target was performed using AutoDock 4.2. Among 26 compounds, 12 phytocompounds were identified to modulate 34 pathways associated with cancer. 4-hydroxy-5,6,7-trimethoxyflavanone and Reticuline showed the maximum interactions with proteins involved in cancer. All 12 compounds obeyed the rule of five and p-methoxybenzaldehyde scored the highest drug-likeness score. Micheline A and Anonaine showed the highest binding affinity with Ubiquitin-protein ligase E3 (MDM2). The current study provides the molecular documentation of phytocompounds from Cananga odorata in the regulation of multi-proteins and pathways associated with progression of cancer (mainly Gastric, Melanoma, Prostate, and Breast cancer), which can be further investigated via wet-lab protocols.