Pycnidione, a fungus-derived agent, induces cell cycle arrest and apoptosis in A549 human lung cancer cells

► Pycnidione was first isolated from fungal Theissenia rogersii 92031201. ► Pycnidione markedly and selectively inhibited lung A549 cancer cell proliferation. ► The G 1 phase cell cycle arrest and apoptosis were induced by pycnidione. ► The levels of cyclins and survivin were significantly attenuated by pycnidione. ► Pycnidione caused ROS formation and disrupted the mitochondrial membrane potential. Pycnidione, a small tropolone first isolated from the fermented broth of Theissenia rogersii 92031201, exhibits antitumor activities through an undefined mechanism. The present study evaluated the effects and mechanisms of pycnidione on the growth and death of A549 human lung cancer cells. Pycnidione significantly inhibited the proliferation of A549 cells in a concentration-dependent manner, with a 50% growth inhibition (GI 50 ) value of approximately 9.3 nM at 48 h. Pycnidione significantly decreased the expression of cyclins D1 and E and induced G 1 -phase cell cycle arrest and a subsequent increase in the sub-G 1 phase population. Pycnidione also markedly reduced the expression of survivin and activated caspase-8 and -3, increased reactive oxygen species (ROS) generation, caused the collapse of the mitochondrial membrane potential (MMP), and enhanced PAI-1 production, thus triggering apoptosis in the A549 cells. Taken together, pycnidione exerts anti-proliferative effects on human lung cancer cells through the induction of cell cycle arrest and apoptosis. Therefore, testing of its effects in vivo is warranted to evaluate its potential as a therapeutic agent against lung cancer.