Abstract

Hepatocellular carcinoma (HCC) stands as a prevalent form of primary liver cancer, distinguished by challenging diagnosis and grim prognoses. Its global mortality rate is on the rise, compounded by the insensitivity of HCC patients to conventional anticancer medications. The dysregulation of the Hippo-YAP signaling pathway closely intertwines with HCC progression, notably marked by a significant elevation in YAP expression within hepatocellular carcinoma. Cepharanthine, derived primarily from the Stephania cephalanta Hayata plant, emerges as a natural compound renowned for its diverse anticancer properties, capable of impeding the proliferation across various cancer cell lines. However, the precise mechanism by which cepharanthine influences HCC cells and its impact on the Hippo-YAP signaling pathway remains elusive. In this investigation, we utilized two distinct HCC cell lines alongside nude mice with xenograft tumors to scrutinize the anti-tumor potential of cepharanthine. Our findings reveal that cepharanthine effectively curbs the proliferation of hepatocellular carcinoma cells, retarding tumor growth. Moreover, it diminishes YAP expression within HCC cells and tumors, instigates YAP phosphorylation, and sequesters YAP within the cytoplasm. Consequently, the transcription and expression of YAP downstream target genes experience a notable decrease. Furthermore, we explored the influence of YAP expression levels on the pharmacodynamics of cepharanthine, leveraging YAP overexpression or knockdown techniques. This experimental strategy confirmed that cepharanthine exerts its anti-hepatoma efficacy by intervening in the Hippo-YAP signaling pathway.