The incidence of
liver cancer, the second leading cause of
cancer-related deaths has increased over the past few decades. Although recent treatments such as
sorafenib are promising in patients with advanced
hepatocellular carcinoma (HCC), the response rates remain poor thereby warranting the identification of novel therapeutic agents against
liver cancer. Herein, we investigated the anti-
cancer effect of
ergosterol (a secondary metabolite in medicinal fungus) pretreatment followed by
amphotericin B (AmB) treatment on
liver cancer cell lines. We demonstrated that pretreatment with a nontoxic dose of
ergosterol synergistically enhanced the cytotoxicity of AmB in both Hep3B and HepJ5 cells. The combination treatment-mediated suppression of
cancer cell viability occurred through
necrosis characterized by disrupted cell membrane and significant amounts of debris accumulation. In addition, we also observed a concomitant increase in
reactive oxygen species (ROS) and LC3-II levels in HepJ5 cells treated with
ergosterol and AmB. Our results suggest that
ergosterol-AmB combination treatment effectively induced necrotic cell death in
cancer cells, and deserves further evaluation for development as an anti-
cancer agent.