Anticancer activity of isoobtusilactone a from Cinnamomum kotoense:: Involvement of apoptosis, cell-cycle dysregulation, mitochondria regulation, and reactive oxygen species
Anticancer activity of isoobtusilactone a from Cinnamomum kotoense:: Involvement of apoptosis, cell-cycle dysregulation, mitochondria regulation, and reactive oxygen species
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DOI：
10.1021/np070620e
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发表时间：
2008-06-01
影响因子：
5.1
通讯作者：
Lin, Rong-Jyh
中科院分区：
文献类型：
--
作者：
Chen, Chung-Yi;Chen, Ching-Hsein;Lin, Rong-Jyh
在这项研究中，我们研究了异钝叶硅内酯 A (IOA)（一种从香辛叶中分离出来的成分）对人非小细胞肺癌 (NSCLC)A549 细胞的抗癌作用。发现IOA可诱导G2-M期停滞、诱导细胞凋亡、增加亚G1期并抑制这些细胞的生长。进一步的研究表明，IOA 对细胞周期的阻断与 p21/WAF1、p27(kip1) 和 p53 水平的增加有关。此外，IOA 触发线粒体凋亡途径，如 Bax/Bcl-2 比率增加所示，导致线粒体膜电位丧失、细胞色素 c 释放、caspase-9 和 caspase-3 激活以及 PARP 裂解。我们还发现活性氧 (ROS) 的产生是 IOA 诱导的 A549 细胞生长抑制的关键介质。在抗氧化剂和 NO 抑制剂研究中，我们发现通过用 N-乙酰半胱氨酸 (NAC)、过氧化氢酶、甘露醇、地塞米松、trolox 或 L-NAME 预处理 A549 细胞，我们可以显着减少 ROS 的 IOA 产生。此外，使用NAC阻断ROS，我们可以显着抑制IOA诱导的抗增殖、抗迁移和抗侵袭。最后我们发现IOA抑制A549细胞的迁移和侵袭。综上所述，这些结果表明IOA对A549细胞具有抗癌作用。
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.