Poncirin Impact on Human HER2 Breast Cancer Cells: Inhibiting Proliferation, Metastasis, and Tumor Growth in Mice Potentially through The PI3K/AKT Pathway

Objective: Breast cancer is a prevalent and heterogeneous disease, with human epidermal growth factor receptor-2 (HER2) overexpression occurring in over 20% of cases. Poncirin, a biologically active flavonone derived from the immature dried fruits of Poncirus trifoliata, is a 7-O-neohesperidoside of isosakuranetin with a well-documented history in traditional Chinese medicine for its health-promoting properties. While the previous research hinted at its potential as an anticancer agent, its specific effects on HER2 overexpressing breast cancer cells remain largely unexplored. The aim of this study is to investigate the specific effects of Poncirin, on HER2 overexpressing breast cancer cells. Materials and Methods: In experimental study, we assessed cell proliferation using the CCK-8 assay and explored cell migration and invasion with transwell assays. Additionally, we evaluated colony formation ability and examined apoptosis through the acridine orange/ethidium bromide (AO/EB) and Annexin V-fluorescein isothiocyanate (FITC)/ propidium iodide (PI) staining methods. The study also delved into the molecular mechanisms involved by scrutinizing the phosphatidylinositol 3-kinase/serine-threonine protein kinase (PI3K/AKT) signaling pathway via Western blotting. Furthermore, the researchers conducted in vivo experiments using mouse models to corroborate the findings in a living organism. Results: Poncirin demonstrated a remarkable ability to selectively inhibit proliferation and metastasis of HER2 overexpressing breast cancer cells. Mechanistically, the compound seemed to exert its effects by modulating the PI3K/AKT signaling pathway, implying its central role in the observed anticancer effects. These findings were further substantiated by in vivo experiments, which consistently showed a reduction in tumor growth when poncirin was administered. Conclusion: This study underscores potential of poncirin as a potent agent for restraining the growth and metastasis of HER2 overexpressing breast cancer cells. The evidence suggests that poncirin efficacy may be attributed to its modulation possibly through PI3K/AKT pathway.