|摘要：||Armillaria mellea is a honey mushroom often used in traditional Chinese medicine “Tien-ma”. Nowadays, this medicinal mushroom is also used as dietary supplement in Western and Eastern countries. Armillarikin is purified from A. mellea. Previously, we found cytotoxicity of armillarik in human leukemia. We wondered whether armillarikin can kill liver and intrahepatic bile duct cancer, the second most deadly cancer in Taiwan in 2012. Here, we found induction of cytotoxicity by armillarikin in human hepatocellular carcinoma (HCC) Huh-7, HA22T and HepG2 cells by alamarBlue® assay and MTS assay. Armillarikin treatment also induced collapse of mitochondria transmembrane potential in these cells. Furthermore, induction of apoptotic cell death by armillarikin was demonstrated by sub G1 chromosomal DNA formation by flow cytometry. This apoptosis induction was inhibited by pan-caspase inhibitor Z-VAD-fmk. According immunoblotting data, we also found armillarikin-induced activation of procaspase-3, procaspase-8 and procaspase-9, and upregulation of apoptosis-related phospho-histone 2 and cell cycle arrest-related phospho-histone 3. In addition, ROS scavengers also inhibited armillarikin-induced apoptosis in human HCC, suggesting ROS formation plays an important role in armillarikin-induced apoptosis in human HCC. Moreover, armillarikin also inhibited wound healing and soft agar assays related to the in vivo carcinogenesis in human HCC. We also found cytotoxicity of armillarikin in Hep3B cells with cancer stem cell characters. In conclusion, we found armillarikin is a potential agent for hepatoma or leukemia treatment. Our study indicates potential cancer therapies by using armillarikin treatment for hepatocellular carcinoma.