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首页> 外文期刊>RSC Advances >Plumbagin induces ROS-mediated apoptosis and cell cycle arrest and inhibits EMT in human cervical carcinoma cells
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Plumbagin induces ROS-mediated apoptosis and cell cycle arrest and inhibits EMT in human cervical carcinoma cells

机译：Plumbagin诱导人宫颈癌细胞中ROS介导的凋亡和细胞周期停滞并抑制EMT

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摘要

Plumbagin, an important phytochemical from the roots of the medicinal plant Plumbago zeylanica ?L. has shown many biological activities. The roots of this plant have been in use in the Indian system of medicine for more than twenty five centuries for treatments of various ailments. It has shown anticancer activities, however, the anticancer and anti-metastatic effects of plumbagin are largely unknown against cervical cancer cells. Herein, we investigated the molecular alterations associated with plumbagin-mediated inhibition of growth, survival and epithelial to mesenchymal transition of human cervical cancer SiHa and HeLa cells. Plumbagin (1–4 μM) caused a significant decrease in the cell viability and increased the cell death in SiHa and Hela cells after 24 and 48 h. Plumbagin also caused strong G2/M and S-G2/M phase cell cycle arrest in SiHa and HeLa cells, respectively which was accompanied by a decrease in the expression of cyclin and CDK levels. The expression levels of both mRNAs and proteins of cyclin B1, A and E2 and CDK 1 and 2 decreased after 24 and 48 h. Plumbagin strongly induced apoptosis along with increased ratio of Bax?:?Bcl2 and cleavage of caspase 3, 9, and PARP. Plumbagin caused a significant increase in reactive oxygen species generation which mediated cell death as it was attenuated by pre-treatment with N -acetyl cysteine. Additionally, we also report for the first time that plumbagin possesses an anti-metastatic effect at non-cytotoxic doses that was accompanied by the modulation of MMP-2, 9, E-cadherin, N-cadherin, β-catenin and vimentin. Taken together, our findings suggest that plumbagin has strong anticancer and anti-metastatic effects against human cervical cancer cells.
机译：羽扇豆（Plumbagin），一种来自药用植物西兰花（Plumbago zeylanica？L）根部的重要植物化学物质。已经显示出许多生物活性。这种植物的根已在印度医学体系中使用了25多个世纪，用于治疗各种疾病。它已经显示出抗癌活性，但是，对于宫颈癌细胞，plumbagin的抗癌和抗转移作用在很大程度上是未知的。在本文中，我们研究了与铅瓜蛋白介导的人类宫颈癌SiHa和HeLa细胞的生长，存活以及上皮向间质转化相关的分子变化。 Plumbagin（1-4μM）导致细胞存活率显着下降，并在24 h和48 h后增加了SiHa和Hela细胞的细胞死亡。 Plumbagin还分别在SiHa和HeLa细胞中引起强烈的G2 / M和S-G2 / M期细胞周期停滞，并伴随着细胞周期蛋白和CDK水平的降低。 24和48小时后，细胞周期蛋白B1，A和E2以及CDK 1和2的mRNA和蛋白表达水平均下降。 Plumbagin强烈诱导凋亡，同时Baxα：βBcl2的比例增加，胱天蛋白酶3、9和PARP裂解。 Plumbagin导致活性氧的产生显着增加，并通过用N-乙酰半胱氨酸预处理减弱了活性氧，从而介导了细胞死亡。此外，我们还首次报道了铅蛋白在非细胞毒性剂量下具有抗转移作用，并伴随着MMP-2、9，E-钙粘蛋白，N-钙粘蛋白，β-连环蛋白和波形蛋白的调节。综上所述，我们的研究结果表明，铅白蛋白对人宫颈癌细胞具有强大的抗癌和抗转移作用。

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