Work

Ailanthone restrains hepatocellular carcinoma progression by inducing ferroptosis and disrupting mitochondrial homeostasis

Year: 2025

Type: article

Abstract: Ailanthone (AIL), a natural compound derived from the Ailanthus species, demonstrates substantial clinical efficacy in managing diverse diseases, notably cancer. Despite this, the precise mechanisms underlying AIL's regulation of hepatocellular carcinoma (HCC) progression remain unclear. Our investigation revealed that AIL effectively suppresses HCC cell proliferation in vitro and in vivo, and inhibits metastasis-related phenotypes in vitro. Mechanistically, we discovered that AIL directly interacted with HSP90, thereby enhancing the ubiquitination of GPX4 proteins. This interaction led to a reduction in GPX4 expression levels and subsequently induced ferroptosis in HCC cells. Furthermore, the combination of AIL with GPX4 inhibitors exhibited a strong synergistic anti-proliferative effect on HCC cells. Collectively, these findings underscore the critical role of the HSP90/GPX4/ferroptosis axis in AIL-mediated inhibition of HCC progression.

Source: Scientific Reports

DOI: 10.1038/s41598-025-26038-5

Authors: Kewen Ye, Zhenghao Zhang, Shanmei Lv, Jintao Wu, Jiaoping Zhao

Institutions: Shaoxing University, Shaoxing People's Hospital

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690