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

Abstract

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 theimmature dried fruits of Poncirus trifoliata, is a 7-O-neohesperidoside of isosakuranetin with a well-documented historyin traditional Chinese medicine for its health-promoting properties. While the previous research hinted at its potentialas an anticancer agent, its specific effects on HER2 overexpressing breast cancer cells remain largely unexplored. Theaim 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 exploredcell migration and invasion with transwell assays. Additionally, we evaluated colony formation ability and examinedapoptosis 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 scrutinizingthe 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 livingorganism.Results: Poncirin demonstrated a remarkable ability to selectively inhibit proliferation and metastasis of HER2overexpressing breast cancer cells. Mechanistically, the compound seemed to exert its effects by modulating thePI3K/AKT signaling pathway, implying its central role in the observed anticancer effects. These findings were furthersubstantiated by in vivo experiments, which consistently showed a reduction in tumor growth when poncirin wasadministered.Conclusion: This study underscores potential of poncirin as a potent agent for restraining the growth and metastasisof HER2 overexpressing breast cancer cells. The evidence suggests that poncirin efficacy may be attributed to itsmodulation possibly through PI3K/AKT pathway.

Keywords

• anticancer effects
• breast cancer
• her2 overexpression
• poncirin