title: Pycnidione, a fungus-derived agent, induces cell cycle arrest and apoptosis in A549 human lung cancer cells.
abstract: 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 9.3nM at 48h. 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.
authors.affiliation: School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Che-Jen
authors.initials: CJ
authors.lastname: Hsiao
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Hsiao
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Chen
authors.forename: Jih-Hwa
authors.initials: JH
authors.lastname: Guh
authors.forename: George
authors.initials: G
authors.lastname: Hsiao
authors.forename: Yen-Ju
authors.initials: YJ
authors.lastname: Chan
authors.forename: Tzong-Huei
authors.initials: TH
authors.lastname: Lee
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Chung
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D005658:Fungi / Q000737:chemistry*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014334:Tropolone / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017395:Plasminogen Activator Inhibitor 1; D017382:Reactive Oxygen Species; D014334:Tropolone; D053148:Caspase 3; D053181:Caspase 8