Z-Guggulsterone Induces Cell Cycle Arrest and Apoptosis by Targeting the p53/CCNB1/PLK1 Pathway in Triple-Negative Breast Cancer

[Image: see text] Myrrh is the dried resin of Commiphora Myrrh Engl., which exerts anticancer properties. However, its effects and molecular mechanisms in triple-negative breast cancer (TNBC) remain unclear. In this study, we used network pharmacology to screen Z-Guggulsterone (Z-GS) as a characteristic active component of myrrh. Cell Counting Kit-8 proliferation assays showed that Z-GS inhibited proliferation of the TNBC cell lines MDA-MB-468 and BT-549. Transwell assays also showed that Z-GS inhibited TNBC migration and invasion phenotypes. Our network pharmacology combined with RNA-sequencing analyses showed that Z-GS affected cell cycle and apoptosis processes in TNBC cells, mainly via p53 signaling, to regulate key CCNB1 (cyclin B1), PLK1 (polo-like kinase 1), and p53 targets. Flow cytometry revealed that Z-GS arrested the cell cycle at the G2/M phase and increased apoptosis in TNBC cells. Western blotting and quantitative real-time polymerase chain reaction studies confirmed that Z-GS functioned via the p53-mediated downregulation of CCNB1 and PLK1 expression. In vivo studies showed that Z-GS effectively inhibited TNBC progression. Collectively, Z-GS exhibited potential anti-TNBC activity and may functions via the p53/CCNB1/PLK1 pathway.