Pycnidione, a fungus-derived agent, induces cell cycle arrest and apoptosis in A549 human lung cancer cells
Journal
Chemico-Biological Interactions
Journal Volume
197
Journal Issue
1
Pages
23-30
Date Issued
2012
Author(s)
Che-Jen Hsiao
Shih-Hsin Hsiao
Wei-Lin Chen
George Hsiao
Yen-Ju Chan
Chi-Li Chung
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 9.3 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. ? 2012 Elsevier Ireland Ltd. All rights reserved.
SDGs
Other Subjects
caspase 3; caspase 8; cyclin D1; cyclin E; microbial products not classified elsewhere; plasminogen activator inhibitor 1; pycnidione; reactive oxygen metabolite; survivin; unclassified drug; antiproliferative activity; apoptosis; article; cancer cell; cancer cell destruction; cell cycle arrest; cell death; cell growth; cell population; cell proliferation; concentration response; controlled study; drug effect; drug isolation; drug mechanism; drug screening; drug structure; enzyme activation; fungus; G1 phase cell cycle checkpoint; human; human cell; in vivo study; lung cancer; mitochondrial membrane potential; protein expression; Theissenia rogersii; Antineoplastic Agents; Apoptosis; Caspase 3; Caspase 8; Cell Cycle Checkpoints; Cell Line, Tumor; Fungi; Humans; Lung Neoplasms; Membrane Potential, Mitochondrial; Plasminogen Activator Inhibitor 1; Reactive Oxygen Species; Tropolone; Fungi
Type
journal article