Yadanziolide A Inhibits Proliferation and Induces Apoptosis of Hepatocellular Carcinoma via JAK-STAT Pathway: A Preclinical Study.

Simple Summary: Liver cancer remains a serious health issue worldwide, necessitating the development of novel treatments. Yadanziolide A (Y-A) has shown potential in treating liver cancer. Our research evaluated Y-A's effects on liver cancer cells and in a mouse model. We discovered that Y-A not only kills liver cancer cells but also prevents their spread and induces programmed cell death at effective doses. In animal models, Y-A reduced tumor growth and improved health markers. Our study also identified that Y-A targets specific pathways related to cancer cell survival and growth, offering insights into its mechanism. These findings support Y-A as a promising candidate for liver cancer therapy, highlighting its effectiveness and potential clinical application. Liver cancer is a significant global health concern, prompting the search for innovative therapeutic solutions. Yadanziolide A (Y-A), a natural derivative of Brucea javanica, has emerged as a promising candidate for cancer treatment; however, its efficacy and underlying mechanisms in liver cancer remain incompletely understood. In this study, we conducted a comprehensive evaluation of Y-A's effects on liver cancer cells using a range of in vitro assays and an orthotopic liver cancer mouse model. Our findings reveal that Y-A exerts dose-dependent cytotoxic effects on liver cancer cells, significantly inhibiting proliferation, migration, and invasion at concentrations ≥ 0.1 μM. Furthermore, Y-A induces apoptosis, as evidenced by increased apoptotic cell populations and apoptosome formation. In vivo studies confirm that Y-A inhibits tumor growth and reduces liver damage in mouse models. Mechanistically, Y-A targets the TNF-α/STAT3 pathway, inhibiting STAT3 and JAK2 phosphorylation, thereby activating apoptotic pathways and suppressing tumor cell growth. These results suggest that Y-A has promising anticancer activity and potential utility in liver cancer therapy. [ABSTRACT FROM AUTHOR]