School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
Toxicol In Vitro. 2011 Oct;25(7):1385-91. doi: 10.1016/j.tiv.2011.05.009. Epub 2011 May 13.
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. MTT assay showed that luteolin had obvious cytotoxicity on A549 with IC(50) of 40.2 μM 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 TNFα, an active agent of NF-κB, showed that pretreatment of A549 cells with luteolin could inhibit TNFα induced trans-nuclear of NF-κB. 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-κB (p65). These results suggested that luteolin might have therapeutic potential against NSCLC.
在这项研究中，我们研究了木樨草素（2-(3,4-二羟基苯基)-5,7-二羟基-4-色原酮）对人非小细胞肺癌细胞系 A549 产生强大细胞周期抑制和促凋亡作用的潜在分子机制。MTT 分析表明，木樨草素对 A549 具有明显的细胞毒性，48 小时的 IC50 为 40.2 μM。Hoechst 33258 染色和 Annexin V-FITC/PI 双染色分析显示木樨草素对 A549 细胞具有促凋亡作用。流式细胞术显示大量凋亡细胞和增加的 G2 期细胞。Western blot 分析表明，木樨草素激活 JNK，增加 Bax，促进 procaspase-9 切割，最终激活 caspase-3。使用 TNFα（NF-κB 的活性物质）的测定表明，用木樨草素预处理 A549 细胞可以抑制 TNFα 诱导的 NF-κB 转核。总之，木樨草素通过 A549 细胞的细胞周期阻滞和凋亡诱导表现出显著的细胞毒性作用。促凋亡作用是通过激活 JNK 和抑制 NF-κB（p65）易位来实现的。这些结果表明，木樨草素可能具有治疗非小细胞肺癌的潜力。
