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芥子提取物通过差异调节细胞凋亡、细胞周期、迁移和侵袭对人肺癌细胞表现出抗增殖作用。

Mustard Seed () Extract Exhibits Antiproliferative Effect against Human Lung Cancer Cells through Differential Regulation of Apoptosis, Cell Cycle, Migration, and Invasion.

机构信息

Department of Pathology, Chonbuk National University Medical School, Jeonju 54907, Korea.

Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef 62511, Egypt.

出版信息

Molecules. 2020 Apr 29;25(9):2069. doi: 10.3390/molecules25092069.

Abstract

Lung cancer is the primary cause of cancer-related death worldwide, and development of novel lung cancer preventive and therapeutic agents are urgently needed. (black mustard) seeds are commonly consumed in several Asian and African countries. Mustard seeds previously exhibited significant anticancer activities against several cancer types. In the present study, we have investigated various cellular and molecular mechanisms of anticancer effects of an ethanolic extract of seeds against A549 and H1299 human non-small cell lung cancer cell lines. extract showed a substantial growth-inhibitory effect as it reduced the viability and clonogenic survival of A549 and H1299 cells in a concentration-dependent manner. extract induced cellular apoptosis in a time- and concentration-dependent fashion as evidenced from increased caspase-3 activity. Furthermore, treatment of both A549 and H1299 cells with extract alone or in combination with camptothecin induced DNA double-strand breaks as evidenced by upregulation of γH2A histone family member X, Fanconi anemia group D2 protein, Fanconi anemia group J protein, ataxia-telangiectesia mutated and Rad3-related protein. Based on cell cycle analysis, extract significantly arrested A549 and H1299 cells at S and G2/M phases. Additionally, extract suppressed the migratory and invasive properties of both cell lines, downregulated the expression of matrix metalloproteinase-2 (MMP2), MMP9, and Snail and upregulated the expression of E-cadherin at mRNA and protein levels. Taken together, these findings indicate that seed extract may have an important anticancer potential against human lung cancer which could be mediated through simultaneous and differential regulation of proliferation, apoptosis, DNA damage, cell cycle, migration, and invasion.

摘要

肺癌是全球癌症相关死亡的主要原因,迫切需要开发新的肺癌预防和治疗药物。(芥菜)种子在几个亚洲和非洲国家被广泛食用。芥子曾对多种癌症表现出显著的抗癌活性。在本研究中,我们研究了种子的乙醇提取物对 A549 和 H1299 人非小细胞肺癌细胞系的各种细胞和分子抗癌作用机制。提取物表现出显著的生长抑制作用,因为它以浓度依赖的方式降低了 A549 和 H1299 细胞的活力和集落形成能力。提取物以时间和浓度依赖的方式诱导细胞凋亡,这从 caspase-3 活性的增加得到证明。此外,用提取物单独或与喜树碱联合处理 A549 和 H1299 细胞会诱导 DNA 双链断裂,这从 γH2A 组蛋白家族成员 X、范可尼贫血组 D2 蛋白、范可尼贫血组 J 蛋白、共济失调毛细血管扩张症突变和 Rad3 相关蛋白的上调得到证明。基于细胞周期分析,提取物显著将 A549 和 H1299 细胞阻滞在 S 和 G2/M 期。此外,提取物抑制了这两种细胞系的迁移和侵袭特性,下调了基质金属蛋白酶-2(MMP2)、MMP9 和 Snail 的表达,并上调了 E-钙黏蛋白在 mRNA 和蛋白水平的表达。综上所述,这些发现表明,种子提取物可能对人类肺癌具有重要的抗癌潜力,其作用机制可能是通过同时和差异调节增殖、凋亡、DNA 损伤、细胞周期、迁移和侵袭来实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eed/7248788/20853625f285/molecules-25-02069-g001.jpg

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