Armillaria mellea component armillarikin induces apoptosis in human leukemia cells

Honey mushroom Armillaria mellea, a commonly used medicinal food in Asia, is an important component of traditional Chinese medicine "Tien-ma". Armillarikin is a compound isolated from A. mellea with unclear biomedical functions. In this study, we found that armillarikin inhibited the viability of human leukemia K562, U937, and HL-60 cells in a concentration-dependent manner, causing cell death mainly attributable to apoptosis accompanied by reduction of mitochondrial transmembrane potential. Armillarikin induced cleavage of caspase-8, caspase-9, caspase-3, and caspase-3 substrate PARP. Armillarikin-induced growth inhibition and apoptosis were reversed by pan-caspase inhibitor Z-VAD-fmk, indicating a caspase-dependent effect. Moreover, armillarikin increased production of intracellular ROS. Prevention of ROS production attenuated armillarikin-induced apoptosis, suggesting mediation by ROS. In conclusion, armillarikin inhibited growth and induced apoptosis through a mechanism involving mitochondria dysfunction, caspase activation and ROS production in human leukemia K562, U937, and HL-60 cells.