Exploring Mechanism of Key Chinese Herbal Medicine on Breast Cancer by Data Mining and Network Pharmacology Methods.

OBJECTIVE: To screen the key Chinese Herbal Medicines (KCHMs) against breast cancer by data mining, and analyze the potential mechanism of KCHMs using network pharmacology method. METHODS: Clinical prescriptions consisted of CHMs for treating breast cancer were screened, and then Traditional Chinese Medicine Inheritance Support System (TCMISS) was applied to obtain the KCHMs. Subsequently, active ingredients and corresponding target genes of KCHMs were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, and target genes of breast cancer were collected using OMIM and MalaCards. After that, the overlapping target genes of KCHMs and breast cancer were screened, and the protein-protein interaction (PPI) network was built. In addition, a network of "KCHMs-active ingredients-breast cancer-targets" was constructed by Cytoscape 3.7.1. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis were performed with Database for Annotation, Visualization and Integrated Discovery (DAVID) database to reveal the action mechanism of KCHMs. RESULTS: A total of 7 KCHMs were identified, whose active ingredients include quercetin, luteolin, nobiletin, kaempferol, isorhamnetin, naringenin, and be-ta-sitosterol, etc. Based on protein-protein interaction analysis, core targets were ESR1, MYC, CCND1, EGFR, CASP3, ERBB2, etc. Several KEGG pathways (e.g, PI3K-Akt, p53, ErbB, and HIF-1 signaling pathways) were found. CONCLUSION: Based on the combination of the data mining method and network pharmacology approach, the therapeutic effect of KCHMs on breast cancer may be realized by acting on target genes and signaling pathways related to the formation and progression of breast cancer.

ß-Asarone suppresses Wnt/ß-catenin signaling to reduce viability, inhibit migration/invasion/adhesion and induce mitochondria-related apoptosis in lung cancer cells.

Lung cancer is the leading cause of cancer death worldwide. Chemotherapy is one of the most effective strategies for lung cancer treatment. However, the side effects of chemotherapy limit the application of chemotherapeutic agents. The ß-Asarone, a low-toxicity natural compound from a traditional Chinese medicinal herb, has been demonstrated to display anticancer activities in multiple cancer types. However, the anticancer activities of ß-Asarone in lung cancer have not been shown, and the underlying molecular mechanisms are still unclear. In the current study, we show that ß-Asarone displays a dose-dependent inhibitory effect on the viability of lung cancer cells. Additionally, ß-Asarone significantly suppresses the cell migration, invasion, and adhesion of lung cancer cells. Moreover, ß-Asarone induces apoptosis associated with the activation of caspase-9 and caspase-3, the upregulation of XAF1, Puma, Bax (Ser184) and Bad (Ser112), the downregulation of XIAP, Bcl-2 and Survivin, the translocation of Bax, Bad, phospho-Bax (Ser184), phospho-Bad (Ser112) and cytochrome C and the reduction of the mitochondrial membrane potential. Mechanistically, our study shows that ß-Asarone inhibits Wnt/ß-catenin signaling. Rescuing the activation of Wnt/ß-catenin signaling overcomes ß-Asarone-induced anticancer effects. Taken together, our data provide the first evidence of the anticancer effects of ß-Asarone in lung cancer, demonstrates that the inhibition of Wnt/ß-catenin signaling could be critical for ß-Asarone-induced anticancer effects. Our study thus suggests a potential application of ß-Asarone as an anticancer agent in the clinical treatment of lung cancer.