Luteolin induced G2 phase cell cycle arrest and apoptosis on non-small cell lung cancer cells
Luteolin induced G2 phase cell cycle arrest and apoptosis on non-small cell lung cancer cells
复制标题
木犀草素诱导非小细胞肺癌细胞G2期细胞周期停滞和细胞凋亡
DOI：
10.1016/j.tiv.2011.05.009
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发表时间：
2011-10-01
影响因子：
3.2
通讯作者：
Cao, Peng
中科院分区：
文献类型：
--
作者：
Cai, Xueting;Ye, Tingmei;Cao, Peng
在这项研究中，我们研究了木犀草素（2-（3,4-二羟基苯基）-5,7-二羟基-4-铬酮）对人非小细胞肺癌A549细胞周期抑制和促凋亡作用的潜在分子机制。MIT实验显示木犀草素对A549细胞具有明显的细胞毒性，48 h时IC50为40.2 μ M。Hoechst 33258染色法和膜联蛋白V-FITC/PI双染色分析证实木犀草素对A549细胞具有促凋亡作用。流式细胞术观察到大量凋亡细胞和增多的G2期细胞。Western blotting结果显示木犀草素激活JNK，增加Bax，促进procaspase-9的裂解，激活caspase-3。利用NF-kappa B的活性因子TNF α检测，木犀草素预处理A549细胞可以抑制TNF fa诱导的NF-kappa B的反核。综上所述，木犀草素在A549细胞中通过阻滞细胞周期和诱导凋亡表现出明显的细胞毒作用。通过激活JNK和抑制NF-kappa B的易位来实现促凋亡作用（p65）。这些结果提示木犀草素可能具有治疗非小细胞肺癌的潜力。(C) 2011 Elsevier Ltd.版权所有。
In this study, we investigated the underlying molecular mechanism for the potent cell cycle inhibition and pro-apoptotic effect of luteolin (2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone) on human non-small-cell lung carcinoma cell line A549. MIT assay showed that luteolin had obvious cytotoxicity on A549 with IC50 of 40.2 mu M at 48 h. Pro-apoptotic effect of luteolin on A549 cells was demonstrated by Hoechst 33258 staining assay and annexin V-FITC/PI double staining analysis. A great quantity of apoptotic cells and increasing G2 phase cells were observed by flow cytometry. Western blotting assay revealed that luteolin activated JNK, increased Bax, promoted procaspase-9 cleavage and activated caspase-3 at last. Assay using TNF alpha, an active agent of NF-kappa B, showed that pretreatment of A549 cells with luteolin could inhibit TNFa induced trans-nuclear of NF-kappa B. In summary, luteolin displayed a significant cytotoxic effect through cell cycle arrest and apoptosis induction in A549 cells. Pro-apoptotic effect was implemented via activating JNK and inhibiting translocation of NF-kappa B (p65). These results suggested that luteolin might have therapeutic potential against NSCLC. (C) 2011 Elsevier Ltd. All rights reserved.