Antrocinol-mediated downregulation of ATG5 induces autophagy-dependent cell death and activates the unfolded protein response through PERK/CHOP signaling in lenvatinib-resistant hepatocellular carcinoma cells

This study provides the first evidence that Antrocinol, a novel hydroxylated derivative of antrocin, synergises with Lenvatinib to exert anti-proliferative effects on Lenvatinib-resistant HCC cells. Our results indicate that Antrocinol may enhance chemosensitivity in HCC by activating the unfolded protein response (UPR) pathway, specifically through the PERK/CHOP axis, and promoting autophagy-dependent cell death. These findings suggest that autophagy acts as a tumor-suppressive mechanism in HCC, with potential therapeutic implications for overcoming drug resistance.