Colorectal cancer (CRC) is one of the major causes of death across the world and incidence rate of CRC increasing alarmingly each passing year. Diet, genomic anomalies, inflammation and deregulated signaling pathways are among the major causes of CRC. Because of numerous side effects of CRC therapies available now, researchers all over the world looking for alternative treatment/preventive strategy with lesser/no side effects. Olive oil which is part of Mediterranean diet contains numerous phenolic compounds that fight against free radicals and inflammation and also well-known for protective role against CRC. The current review focused on the recent evidences where olive oil and its phenolic compounds such as Hydroxytyrosol, Oleuropein and Oleocanthal showed activities against CRC as well to analyze the cellular and molecular signaling mechanism through which these compounds act on. These compounds shown to combat CRC by reducing proliferation, migration, invasion, and angiogenesis through regulation of numerous signaling pathways including MAPK pathway, PI3K-Akt pathway, and Wnt/β-catenin pathway etc. and at the same time induce apoptosis in different CRC model. However, further research is an absolute necessity to establish these compounds as nutritional supplements and develop therapeutic strategy in CRC.
Apigenin, a natural flavonoid, has shown early promise in colon cancer (CC); thus, exploring potential mechanisms of apigenin in CC is obligatory. In this study, shared targets of apigenin and CC were identified through different online tools and subjected to functional enrichment analyses like Gene Ontology and KEGG. Further, the protein-protein interaction network of the shared targets was developed (via STRING); hub/core targets were identified (MCODE application). The top targets of apigenin in CC were identified by molecular docking; further investigated for differential gene and protein expression in CC and their influence on CC patient survival (using TCGA data). Based on the docking score of the 13 hub genes, the top 3 targets (HSP90AA1, MMP9, PTGS2) were selected, and their expression was significantly elevated and related to poor overall survival in CC (except PTGS2). Molecular dynamics simulation further validated protein-ligand interactions and selected HSP90AA1 as the best target of apigenin in CC. Finally, apigenin was found to be involved in the cytotoxicity of CC cells (COLO-205) by reducing HSP90AA1 expression. The results of this study identified HSP90AA1 as one of the prime targets of apigenin in CC, and apigenin might act on HSP90AA1 to exert its anti-cancer mechanism.
Protein tyrosine phosphatase 1B (PTP1B) has emerged as one of the links between obesity and colon cancer (CC). Anti‐obesity and anti‐CC attributes of sweet potato (Ipomoea batatas) reported sparsely. Here, we aimed to study the potential of PTP1B as a target in CC, particularly in obese population. Expression and genomic alteration frequency of PTPN1 (PTP1B) were checked in CC. Interacting partners of PTP1B through STRING and hub genes through Cytoscape (MCODE) were identified. Hub genes were subjected to functional enrichment analyses (via Metascape), differential gene expression, copy number variation, and single nucleotide variation analyses (GSCA database). Cancer‐related pathways and associated immune infiltrates of the hub genes were checked too. Eleven sweet potato‐derived compounds selected through drug likeness (DL) and toxicity filters were explored via molecular docking (AutoDock Vina) to reveal the interactions with PTP1B. Genomic alteration frequency of the PTPN1 was highest in CC compared to all the other TCGA cancers, and a high expression (RNA and protein) is also observed in CC that correlated well to a poor overall survival (OS). Furthermore, PTP1B and related proteins were enriched in different biological processes and signaling pathways related to carcinogenesis including epithelial–mesenchymal transition. Overall, PTP1B identified as a potential target in obesity‐linked CC and sweet potato might exert its protective action by targeting the PTP1B. Sweet potato compounds (e.g., pelargonidin and luteolin) interacted with the catalytic P loop and the WPD loop of the PTP1B. Furthermore, MD simulation study ascertained that luteolin has the highest affinity against the PTP1B, whereas pelargonidin and quercetin showed good binding affinity too, thus can be explored further.
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