A Novel Role for Lupeol in Hepatocellular Carcinoma Treatment via Promoting Autophagy to Suppress Exosome Secretion.

Hepatocellular carcinoma (HCC) is a highly lethal malignancy presenting a considerable challenge due to limited therapeutic options. This study investigates the anti-cancer mechanisms of Lupeol, a natural triterpenoid. Our results demonstrated that Lupeol exhibited significant anti-proliferative effects on HepG2 cells with an IC of 42.82 μM at 24 h. Furthermore, Lupeol treatment significantly inhibited cell migration and suppressed the secretion of exosomes, as evidenced by the downregulation of exosome markers (CD63, TSG101) ( < 0.05). Mechanistic analysis revealed that Lupeol induces autophagy, marked by the upregulation of LC3-II and Beclin-1. Importantly, blocking autophagy with the inhibitor 3-MA prevented the Lupeol-induced reduction of CD63 and restored exosome secretion ( < 0.05). These findings suggest that Lupeol inhibits HCC progression by inducing autophagy to suppress exosome secretion, rather than merely acting as a correlative factor. This study elucidates a novel mechanism where Lupeol redirects multivesicular bodies toward the autophagic-lysosomal pathway, highlighting its potential as an effective therapeutic strategy for HCC.