Anticancer effects of epigallocatechin-3-gallate nanoemulsion on lung cancer cells through the activation of AMP-activated protein kinase signaling pathway
Anticancer effects of epigallocatechin-3-gallate nanoemulsion on lung cancer cells through the activation of AMP-activated protein kinase signaling pathway
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DOI：
10.1038/s41598-020-62136-2
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发表时间：
2020-03-20
影响因子：
4.6
通讯作者：
Wang, Chi-Chung
中科院分区：
文献类型：
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作者：
Chen, Bing-Huei;Hsieh, Chia-Hung;Wang, Chi-Chung
表没食子儿茶素 - 3 - 没食子酸酯（EGCG）是一种源自绿茶的多酚，具有抗肿瘤活性。制备了一种EGCG纳米乳液（纳米 - EGCG）以提高EGCG的稳定性并减少其副作用，用于治疗人肺癌细胞，并对其抗肿瘤效果进行了研究。还阐明了其对培养的人肺癌细胞产生抗肿瘤作用的可能分子机制。采用甲基噻唑基四唑溴盐（MTT）、集落形成、迁移和侵袭实验测定了EGCG和纳米 - EGCG的抗肿瘤效果。此外，利用蛋白质印迹分析研究了腺苷酸活化蛋白激酶（AMPK）信号通路的变化。使用AMPK抑制剂来确定AMPK信号通路在纳米 - EGCG分子机制中所起的作用。我们的结果表明，EGCG和纳米 - EGCG均抑制H1299肺癌细胞的生长，半数抑制浓度分别为36.03和4.71 μM。此外，纳米 - EGCG以剂量依赖的方式有效抑制肺癌细胞集落形成、迁移和侵袭。纳米 - EGCG可能通过不依赖基质金属蛋白酶（MMP） - 2和MMP - 9的机制抑制肺癌细胞侵袭。此外，纳米 - EGCG调节了AMPK信号通路中几种关键调节蛋白的表达。纳米 - EGCG可能通过激活AMPK信号通路抑制肺癌细胞增殖、集落形成、迁移和侵袭。纳米 - EGCG的这种新机制表明其在肺癌预防和治疗中的应用。我们的结果为进一步研究其在体内的潜在活性和作用提供了实验基础。
Epigallocatechin-3-gallate (EGCG), a green tea-derived polyphenol, exhibits antitumor activities. An EGCG nanoemulsion (nano-EGCG) was prepared to improve the stability and reduce the side effects of EGCG for treatment of human lung cancer cells, and the antitumor effects were studied. The possible molecular mechanism underlying its antitumor effects on cultured human lung cancer cells was also elucidated. The antitumor effects of EGCG and nano-EGCG were determined using methylthiazolyldiphenyl-tetrazolium bromide (MTT), colony formation, migration, and invasion assays. In addition, changes in the AMP-activated protein kinase (AMPK) signaling pathway were investigated using Western blot analyses. AMPK inhibitors were used to determine the roles of the AMPK signaling pathway involved in the molecular mechanism of the nano-EGCG. Our results showed that both EGCG and nano-EGCG inhibited the growth of H1299 lung cancer cells, with half-maximal inhibitory concentrations of 36.03 and 4.71 mu M, respectively. Additionally, nano-EGCG effectively suppressed lung cancer cell colony formation, migration, and invasion in a dose-dependent manner. Nano-EGCG may inhibit lung cancer cell invasion through matrix metalloproteinase (MMP)-2- and MMP-9-independent mechanisms. Furthermore, the expression of several key regulatory proteins in the AMPK signaling pathway was modulated by nano-EGCG. Nano-EGCG may inhibit lung cancer cell proliferation, colony formation, migration, and invasion through the activation of AMPK signaling pathways. This novel mechanism of nano-EGCG suggests its application in lung cancer prevention and treatment. Our results provide an experimental foundation for further research on its potential activities and effects in vivo.