Scoparone inhibits pancreatic cancer through PI3K/Akt signaling pathway

Computational and Mathematical Methods in Medicine

et al. 2022

Traditional Chinese medicine (TCM) is applied in the anticancer adjuvant therapy of various malignancies and pancreatic cancer included. Xiaoji recipe consists several TCM materials with anticancer activities. In our work, we intended to analyze the molecular targets as well as the underlying mechanisms of Xiaoji recipe against pancreatic cancer. A total of 32 active components and 522 potential targets of Xiaoji recipe were selected using the TCMSP and SwissTargetPrediction databases. The potential target gene prediction in pancreatic cancer was performed using OMIM, Disgenet, and Genecards databases, and totally, 998 target genes were obtained. The component-disease network was constructed using the Cytoscape software, and 116 shared targets of pancreatic cancer and Xiaoji recipe were screened out. As shown in the protein–protein interaction (PPI) network, the top 20 hub genes such as TP53, HRAS, AKT1, VEGFA, STAT3, EGFR, and SRC were further selected by degree. GO and KEGG functional enrichment analysis revealed that Xiaoji recipe may affect pancreatic cancer progression by targeting the PI3K/AKT and MAPK signaling pathways. Moreover, we performed in vitro assays to explore the effect of Xiaoji recipe on pancreatic cancer cells. The results revealed that Xiaoji recipe suppressed the viability and migration and promoted the apoptosis of pancreatic cancer cells via the inactivation of PI3K/AKT, MAPK, and STAT3 pathways. The findings of our study suggested the potential of Xiaoji recipe in the targeting therapy of pancreatic cancer.

Section: Introductionmentioning

confidence: 99%

Identification of Molecular Targets and Underlying Mechanisms of Xiaoji Recipe against Pancreatic Cancer Based on Network Pharmacology

Xia

Chen

Computational and Mathematical Methods in Medicine

et al. 2022

“…Preset all available gene sets, p -value cutoff (FDR, adjusted in the hypergeometric test) < 0.05 and show the top 30 pathways. Finally, the candidate drugs from the STITCH database are screened out from the enrichment results.STITCH ( Li et al, 2021 ) ( http://stitch.embl.de/ ) is a powerful search tool for predicting drug-target relationships. In this analysis, we used 42 genes shared by COVID-19 and COPD to predict drug candidates for COVID-19 and COPD comorbidities.…”

Section: Methodsmentioning

confidence: 99%

Host Factor Interaction Networks Identified by Integrative Bioinformatics Analysis Reveals Therapeutic Implications in COPD Patients With COVID-19

Zheng

et al. 2021

Front. Pharmacol.

Background: The COVID-19 pandemic poses an imminent threat to humanity, especially for those who have comorbidities. Evidence of COVID-19 and COPD comorbidities is accumulating. However, data revealing the molecular mechanism of COVID-19 and COPD comorbid diseases is limited.Methods: We got COVID-19/COPD -related genes from different databases by restricted screening conditions (top500), respectively, and then supplemented with COVID-19/COPD-associated genes (FDR<0.05, |LogFC|≥1) from clinical sample data sets. By taking the intersection, 42 co-morbid host factors for COVID-19 and COPD were finally obtained. On the basis of shared host factors, we conducted a series of bioinformatics analysis, including protein-protein interaction analysis, gene ontology and pathway enrichment analysis, transcription factor-gene interaction network analysis, gene-microRNA co-regulatory network analysis, tissue-specific enrichment analysis and candidate drug prediction.Results: We revealed the comorbidity mechanism of COVID-19 and COPD from the perspective of host factor interaction, obtained the top ten gene and 3 modules with different biological functions. Furthermore, we have obtained the signaling pathways and concluded that dexamethasone, estradiol, progesterone, and nitric oxide shows effective interventions.Conclusion: This study revealed host factor interaction networks for COVID-19 and COPD, which could confirm the potential drugs for treating the comorbidity, ultimately, enhancing the management of the respiratory disease.

“…Scopolone is a traditional Chinese medicine phenylpropane monomer. It has a wide range of pharmacological activities, and its antitumor activity has been confirmed in leukemia, laryngeal cancer, and prostate cancer [ 24 , 25 ]. However, we still need to continue to study and use more convincing evidence to explain the potential molecular mechanism of its antitumor activity.…”

Section: Discussionmentioning

confidence: 99%

6,7-Dimethoxycoumarin Influences the Erythroid Differentiation of Human Chronic Myelogenous Leukemia K562 Cells through Regulating FOXO3/p27 Signal Pathway

et al. 2022

Journal of Oncology

Objective. To study the pharmacological activity and the mechanism of action of natural compounds derived from 6,7-dimethoxycoumarin on the differentiation of human chronic myeloid leukemia K562 cells. Methods. We use MTT assay (Sigma-Aldrich, USA) to detect cell viability; use flow cytometry to analyze DNA content for cell cycle analysis; use benzidine staining to synthesize hemoglobin to determine K562 cell differentiation; use western blot analysis and qPCR to detect the expression levels of FOX03, P27, CDK4, and their phosphorylation; and use the AOBS laser scanning confocal system (Leica, Wetzlar, Germany) to analyze and quantify the number of positive green spots. The statistical methods used are one-way analysis of variance (ANOVA) and Dunnett’s test to analyze within and between groups. Results. In order to explore the effect of 6,7-dimethoxycoumarin on the differentiation of K562 cell erythrocytes, it was concluded that 6,7-dimethoxycoumarin promotes the differentiation of K562 cell erythrocytes; the proliferation of K562 cells was detected by MTT method, and the results showed that 6,7-dimethoxycoumarin can inhibit the proliferation of K562 cells; to evaluate the effect of 6,7-dimethoxycoumarin on the proliferation of K562 cells, the results showed that 6,7-dimethoxycoumarin increased the expression of FOXO3, P27, CDK4, and CDK65, and decreased the phosphorylation of CDK4 and CDK6 proteins. To further explore the effect of knocking out FOXO3 on cell differentiation, the results show that 6,7-dimethoxycoumarin can reduce the differentiation and proliferation of K562 cells by increasing the expression of FOXO3. Conclusion. This study extended the understanding of the pharmacological activity of 6,7-dimethoxycoumarin and may provide a potential new target for the treatment of chronic myelogenous leukemia. However, we still need to further study the specific molecular capabilities of 6.7 dimethylcoumarin to understand their possible capture mechanism.