In vitro Antiproliferative and Apoptosis Inducing Effect of Allium atroviolaceum Bulb Extract on Breast, Cervical, and Liver Cancer Cells.
In vitro Antiproliferative and Apoptosis Inducing Effect of Allium atroviolaceum Bulb Extract on Breast, Cervical, and Liver Cancer Cells.
复制标题
体外抗增殖和凋亡诱导葱型主动脉菌鳞茎提取物对乳腺癌，宫颈癌和肝癌细胞的作用。
DOI：
10.3389/fphar.2017.00005
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发表时间：
2017
影响因子：
5.6
通讯作者：
Ismail P
中科院分区：
文献类型：
--
作者：
Khazaei S;Esa NM;Ramachandran V;Hamid RA;Pandurangan AK;Etemad A;Ismail P
天然产物被认为是新药发现和开发的有力来源。本研究利用传统中药中天然化合物的多种治疗作用，对葱白鳞茎在MCF 7、MDA-MB-231、HeLa和HepG 2细胞系中的细胞毒活性进行评价。采用甲醇提取法对A.结果表明，阿托品是一种有效的细胞增殖抑制剂，且呈时间和剂量依赖性。流式细胞仪检测DNA含量显示MCF-7细胞阻滞于S期和G2/M期，与Cdk 1下调相关; MDA-MB-231细胞阻滞于S期，与Cdk 1和p53相关; HeLa细胞阻滞于亚G 0期，与Cdk 1下调相关; HepG 2细胞阻滞于G 0/G1、S、G2/M期，与p53相关。细胞形态学研究、半胱氨酸蛋白酶活性测定以及凋亡相关基因Bcl-2的表达证实了细胞凋亡是细胞死亡的机制。Caspase-8、Caspase-9和Caspase-3的活性与Bcl-2的下调一起说明MCF 7中存在内源性和外源性途径，而Caspase-3和Caspase-8的活性显示了细胞凋亡的外源性途径，尽管Bcl-2下调。在HeLa细胞中，caspase-9和caspase-3的活性以及Bcl-2的下调表现为内源性途径或线粒体途径，而HepG 2则表现为caspase非依赖性凋亡。此外，在大多数浓度下，提取物与他莫昔芬的组合对抗MCF 7和MDA-MB-231以及与多柔比星的组合对抗HeLa和HeG 2表现出协同效应，表明A.阿托品单独或与其它药物联合可用于治疗癌症。
Natural products are considered potent sources for novel drug discovery and development. The multiple therapeutic effects of natural compounds in traditional medicine motivate us to evaluate the cytotoxic activity of bulb of Allium atroviolaceum in MCF7 and MDA-MB-231, HeLa and HepG2 cell lines. The bulb methanol extract of A. atroviolaceum was found to be an active cell proliferation inhibitor at the time and dose dependent manner. Determination of DNA content by flow cytometry demonstrated S and G2/M phase arrest of MCF-7 cell, correlated to Cdk1 downregulation, S phase arrest in MDA-MB-231 which is p53 and Cdk1-dependent, sub-G0 cell cycle arrest in HeLa aligned with Cdk1 downregulation, G0/G1, S, G2/M phase arrest in HepG2 which is p53-dependent. Apoptosis as the mechanism of cell death was confirmed by morphology study, caspases activity assay, as well as apoptosis related gene expression, Bcl-2. Caspase-8, -9, and -3 activity with downregulation of Bcl-2 illustrated occurrence of both intrinsic and extrinsic pathways in MCF7, while caspase-3 and -8 activity revealed extrinsic pathway of apoptosis, although Bcl-2 downregulated. In HeLa cells, the activity of caspase-9 and -3 and downregulation of Bcl-2 shows intrinsic pathway or mitochondrial pathway, whereas HepG2 shows caspase independent apoptosis. Further, the combination of the extract with tamoxifen against MCF7 and MDA-MB-231 and combination with doxorubicin against HeLa and HeG2 demonstrated synergistic effect in most concentrations, suggests that the bulb of A. atroviolaceum may be useful for the treatment of cancer lonely or in combination with other drugs.