Anticancer Activity of Isoobtusilactone A from Cinnamomum kotoense: Involvement of Apoptosis, Cell-Cycle Dysregulation, Mitochondria Regulation, and Reactive Oxygen Species

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• 作者：Chung-Yi Chen ; Ching-Hsein Chen ; Yi-Ching Lo ; Bin-Nan Wu ; Hui-Min Wang ; Wen-Li Lo ; Chuan-Min Yen ; Rong-Jyh Lin
• 刊名：Journal of Natural Products
• 出版年：2008
• 出版时间：June 2008
• 年：2008
• 卷：71
• 期：6
• 页码：933 - 940
• 全文大小：899K
• 年卷期：v.71,no.6(June 2008)
• ISSN：1520-6025

文摘

In this study, we investigate the anticancer effect of isoobtusilactone A (IOA), a constituent isolated from the leaves of Cinnamomum kotoense, on human non-small cell lung cancer (NSCLC) A549 cells. IOA was found to induce the arrest of G2-M phase, induce apoptosis, increase sub-G1, and inhibit the growth of these cells. Further investigation revealed that IOA’s blockade of the cell cycle was associated with increased levels of p21/WAF1, p27^kip1, and p53. In addition, IOA triggered the mitochondrial apoptotic pathway, as indicated by an increase in Bax/Bcl-2 ratios, resulting in a loss of mitochondrial membrane potential, release of cytochrome c, activation of caspase-9 and caspase-3, and cleavage of PARP. We also found the generation of reactive oxygen species (ROS) to be a critical mediator in IOA-induced inhibition of A549 cell growth. In antioxidant and NO inhibitor studies, we found that by pretreating A549 cells with either N-acetylcystenine (NAC), catalase, mannitol, dexamethasone, trolox, or L-NAME we could significantly decrease IOA production of ROS. Moreover, using NAC to block ROS, we could significantly suppress IOA-induced antiproliferation, antimigration, and anti-invasion. Finally, we found that IOA inhibited the migration and invasion of A549 cell migration and invasion. Taken together, these results suggest that IOA has anticancer effects on A549 cells.