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Sulforaphene induces apoptosis and inhibits the invasion of esophageal cancer cells through MSK2/CREB/Bcl-2 and cadherin pathway in vivo and in vitro.
Cancer Cell International ( IF 5.3 ) Pub Date : 2019-12-19 , DOI: 10.1186/s12935-019-1061-1
Chengjuan Zhang 1, 2 , Junxia Zhang 3 , Qiong Wu 4, 5 , Benling Xu 6 , Guoguo Jin 7 , Yan Qiao 2, 4 , Simin Zhao 2, 4 , Yang Yang 8 , Jinwen Shang 1 , Xiaofang Li 9 , Kangdong Liu 4, 5, 6
Affiliation  

Background As a novel type of isothiocyanate derived from radish seeds from cruciferous vegetables, sulforaphene (SFE, 4-methylsufinyl-3-butenyl isothiocyanate) has various important biological effects, such as anti-oxidative and anti-bacterial effects. Recently, sulforaphene has attracted increasing attention for its anti-tumor effects and its ability to suppress the development of multiple tumors through different regulatory mechanisms. However, it has not yet been widely investigated for the treatment of esophageal cancer. Methods We observed an increased apoptosis in esophageal cancer cells on sulforaphene treatment through flow cytometry (FCM) analysis and transmission electron microscopy (TEM). Through mass spectrometry (MS) analysis, we further detected global changes in the proteomes and phosphoproteomes of esophageal cancer cells on sulforaphene treatment. The molecular mechanism of sulforaphene was verified by western blot,the effect and mechanism of SFE on esophageal cancer was further verified by patient-derived xenograft mouse model. Results We identified multiple cellular processes that were changed after sulforaphene treatment by proteomics. We found that sulforaphene could repress the phosphorylation of CREB through MSK2, leading to suppression of Bcl-2 and further promoted cell apoptosis. Additionally, we confirmed that sulforaphene induces tumor cell apoptosis in mice. Interestingly, we also observed the obvious inhibition of cell migration and invasion caused by sulforaphene treatment by inhibiting the expression of cadherin, indicating the complex effects of sulforaphene on the development of esophageal cancer. Conclusions Our data demonstrated that sulforaphene induced cell apoptosis and inhibits the invasion of esophageal cancer through a mechanism involving the inhibition of the MSK2-CREB-Bcl2 and cadherin pathway. Sulforaphene could therefore serve as a promising anti-tumor drug for the treatment of esophageal cancer.

中文翻译:

Sulforaphene 在体内和体外通过 MSK2/CREB/Bcl-2 和 cadherin 通路诱导细胞凋亡并抑制食管癌细胞的侵袭。

背景作为一种从十字花科蔬菜萝卜籽中提取的新型异硫氰酸酯,萝卜硫素(SFE,4-methylsufinyl-3-butenyl isothiocyanate)具有多种重要的生物学作用,如抗氧化和抗菌作用。最近,萝卜硫素因其抗肿瘤作用和通过不同调控机制抑制多种肿瘤发展的能力而受到越来越多的关注。然而,它尚未被广泛研究用于治疗食管癌。方法 我们通过流式细胞术 (FCM) 分析和透射电子显微镜 (TEM) 观察到在萝卜硫素治疗后食管癌细胞凋亡增加。通过质谱 (MS) 分析,我们进一步检测了萝卜硫素治疗食管癌细胞蛋白质组和磷酸化蛋白质组的整体变化。通过western blot验证萝卜硫素的分子机制,通过患者来源的异种移植小鼠模型进一步验证SFE对食管癌的作用和机制。结果 我们通过蛋白质组学鉴定了在萝卜硫素处理后发生变化的多个细胞过程。我们发现萝卜硫素可以通过 MSK2 抑制 CREB ​​的磷酸化,从而抑制 Bcl-2 并进一步促进细胞凋亡。此外,我们证实萝卜硫素可诱导小鼠肿瘤细胞凋亡。有趣的是,我们还观察到萝卜硫素通过抑制钙粘蛋白的表达,明显抑制了细胞迁移和侵袭,表明萝卜硫素对食管癌发展的复杂影响。结论 我们的数据表明,萝卜硫素通过抑制 MSK2-CREB-Bcl2 和钙粘蛋白通路的机制诱导细胞凋亡并抑制食管癌的侵袭。因此,萝卜硫素可作为治疗食管癌的有前途的抗肿瘤药物。
更新日期:2019-12-19
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