Evodiae fructus (EF) is a traditional Chinese medicine which is widely used for the treatment of obesity, inflammation, cardiovascular disease, and diseases of the central nervous system. Recent studies have demonstrated the anticancer property of EF, but the active compounds of EF against prostate cancer and its underlying mechanism remain unknown. In this study, a network pharmacology-based approach was used to explore the multiple ingredients and targets of EF. Through protein-protein interaction (PPI), Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, the potential targets and corresponding ingredients of EF against prostate cancer cells were obtained. CCK8 and colony formation assays were performed to evaluate the antiproliferative effect of the active compounds on DU145 cells. Cell cycle analysis, Annexin V-FITC/PI staining assay, and Hoechst 33258 staining assay were used to explore the way of evodiamine-induced cell death. The capacities of cell migration after evodiamine treatment were evaluated by wound-healing assay. PharmMapper database was used to predict the potential targets of evodiamine against cancer cell migration. Western blot assay was performed to investigate the signaling pathway through which evodiamine inhibits cell proliferation and migration. The binding of evodiamine to PI3K and AKT was verified by molecular docking. As a consequence, 24 active compounds and 141 corresponding targets were obtained through a network pharmacology-based approach. The results of PPI analysis, GO enrichment, and KEGG pathway enrichment indicated that molecules in the PI3K/AKT/NF-κB signaling pathway were the potential targets of EF against prostate cancer, and evodiamine was the potential active compound. In vitro study demonstrated that evodiamine displays antiproliferative effect on DU145 cells obviously. Evodiamine induces G2/M cell cycle arrest by Cdc25c/CDK1/cyclin B1 signaling. Additionally, evodiamine also promotes mitochondrial apoptosis and inhibits cell migration through PI3K/AKT/NF-κB signaling in DU145 cells. In conclusion, evodiamine is the active compound of EF to inhibit proliferation and migration of prostate cancer through PI3K/AKT/NF-κB signaling pathway, indicating that evodiamine may serve as a potential lead drug for prostate cancer treatment.
Background:
Cervical cancer is the fourth most prevalent gynecological cancer worldwide, which threatens women's health and causes cancer-related mortality. In the search for effective anticervical cancer drugs, we discovered that β-estradiol (E2), a patent drug for estrogen deficiency syndrome treatment, displays the most potent cytotoxicity against HeLa cells.
Objective:
This study aims to evaluate the growth inhibitory effect of β-estradiol on HeLa cells and explore its underlying mechanisms.
Methods:
CCK-8 assay was used to evaluate the cytotoxicity of 6 compounds against HeLa cells. Flow cytometric analysis and Hoechst 33258 staining assay were performed to detect cell cycle arrest and apoptosis induction. The collapse of the mitochondrial potential was observed by the JC-1 staining assay. The expression levels of proteins were examined by western blotting.
Results:
β-Estradiol, at high concentration, displays potent cytotoxicity against HeLa cells with an IC50 value of 18.71 ± 1.57 μM for 72 h treatment. β-Estradiol induces G2/M cell cycle arrest through downregulating Cyclin B1 and p-CDK1. In addition, β-estradiol-induced apoptosis is accompanied by the loss of mitochondrial potential, activation of the Caspase family, and altered Bax/Bcl-2 ratio. β-Estradiol markedly decreased the expression level of p-AKT and p-NF-κB.
Conclusion:
This study demonstrated that β-estradiol induces mitochondrial apoptosis in cervical cancer through the suppression of the AKT/NF-κB signaling pathway, indicating that β-estradiol may serve as a potential agent for cervical cancer treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.