Cephalochromin Induces G0/G1 Cell Cycle Arrest and Apoptosis in A549 Human Non-Small-Cell Lung Cancer Cells by Inflicting Mitochondrial Disruption

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• 作者：Che-Jen Hsiao ; George Hsiao ; Wei-Lin Chen ; Shih-Wei Wang ; Chun-Ping Chiang ; Li-Ya Liu ; Jih-Hwa Guh ; Tzong-Huei Lee ; Chi-Li Chung
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：April 25, 2014
• 年：2014
• 卷：77
• 期：4
• 页码：758-765
• 全文大小：396K
• 年卷期：v.77,no.4(April 25, 2014)
• ISSN：1520-6025

文摘

The fungus-derived compound cephalochromin, isolated from the fermented broth of Cosmospora vilior YMJ89051501, shows growth-inhibitory and apoptotic activity against human lung cancer A549 cells in a concentration-dependent manner with an IC₅₀ value of 2.8 渭M at 48 h. Cephalochromin induced cell cycle arrest at the G0/G1 phase through down-regulation of cyclin D1, cyclin E, Cdk 2, and Cdk 4 expressions. Cephalochromin markedly increased the hypodiploid sub-G1 phase (apoptosis) of the cell cycle at 48 h as measured by flow cytometric analysis. Reactive oxygen species generation and loss of the mitochondrial membrane potential (MMP) were also markedly induced by cephalochromin. Moreover, the immunoblotting assays showed that cephalochromin reduced survivin and Bcl-xL expression and induced the activation of caspase-8, -9, and -3 and the cleavage of poly(ADP-ribose) polymerase, indicating the involvement of a caspase signaling cascade. The caspase inhibitor Z-VAD-fmk significantly suppressed cephalochromin-induced apoptosis. Cephalochromin also triggered LC3 II, autophagic marker, expression. Taken together, this is the first report that cephalochromin induced an antiproliferative effect on human lung cancer cells through mitochondrial disruption and down-regulation of survivin, leading to cell cycle arrest at the G0/G1 phase, loss of MMP, and subsequently apoptotic cell death.