阿月浑子果肉提取物中的植物化学物质通过抑制 AKT/mTOR 通路和调节 Bcl-2 家族蛋白诱导人三阴性乳腺癌细胞凋亡。

Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins.

机构信息

Chancellor, Era's Lucknow Medical College and Hospital, Era University, Lucknow, 226003, India.

Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, 226003, India.

出版信息

Sci Rep. 2021 May 14;11(1):10322. doi: 10.1038/s41598-021-89420-z.

Abstract

Ajwa dates (Phoenix dactylifera L.) have been described in traditional and alternative medicine to provide several health benefits, but their mechanism of apoptosis induction against human triple-negative breast cancer MDA-MB-231 cells remains to be investigated. In this study, we analyzed the phytoconstituents in ethanolic Ajwa Dates Pulp Extract (ADPE) by liquid chromatography-mass spectrometry (LC-MS) and investigated anticancer effects against MDA-MB-231 cells. LC-MS analysis revealed that ADPE contained phytocomponents belonging to classes such as carbohydrates, phenolics, flavonoids and terpenoids. MTT assay demonstrated statistically significant dose- and time-dependent inhibition of MDA-MB-231 cells with IC values of 17.45 and 16.67 mg/mL at 24 and 48 h, respectively. Hoechst 33342 dye and DNA fragmentation data showed apoptotic cell death while AO/PI and Annexin V-FITC data revealed cells in late apoptosis at higher doses of ADPE. More importantly, ADPE prompted reactive oxygen species (ROS) induced alterations in mitochondrial membrane potential (MMP) in ADPE treated MDA-MB-231 cells. Cell cycle analysis demonstrated that ADPE induced cell arrest in S and G2/M checkpoints. ADPE upregulated the p53, Bax and cleaved caspase-3, thereby leading to the downregulation of Bcl-2 and AKT/mTOR pathway. ADPE did not show any significant toxicity on normal human peripheral blood mononuclear cells which suggests its safe application to biological systems under study. Thus, ADPE has the potential to be used as an adjunct to the mainline of treatment against breast cancer.

摘要

阿月浑子(Phoenix dactylifera L.)在传统和替代医学中被描述为具有多种健康益处,但它们诱导人三阴性乳腺癌 MDA-MB-231 细胞凋亡的机制仍有待研究。在这项研究中,我们通过液相色谱-质谱法(LC-MS)分析了乙醇阿月浑子果肉提取物(ADPE)中的植物成分,并研究了其对 MDA-MB-231 细胞的抗癌作用。LC-MS 分析显示,ADPE 含有属于碳水化合物、酚类、类黄酮和萜烯类等类别的植物成分。MTT 测定表明,ADPE 对 MDA-MB-231 细胞具有显著的剂量和时间依赖性抑制作用,在 24 和 48 小时的 IC 值分别为 17.45 和 16.67mg/mL。Hoechst 33342 染料和 DNA 片段化数据显示细胞发生凋亡性死亡,而 AO/PI 和 Annexin V-FITC 数据显示在较高剂量的 ADPE 下细胞处于晚期凋亡。更重要的是,ADPE 促使活性氧(ROS)诱导 ADPE 处理的 MDA-MB-231 细胞中线粒体膜电位(MMP)的改变。细胞周期分析表明,ADPE 诱导细胞在 S 和 G2/M 检查点停滞。ADPE 上调了 p53、Bax 和裂解的 caspase-3,从而下调了 Bcl-2 和 AKT/mTOR 通路。ADPE 对正常人外周血单个核细胞没有显示出任何显著的毒性,这表明它可以安全地应用于所研究的生物系统。因此,ADPE 有可能作为治疗乳腺癌的主要方法的辅助手段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f7/8121835/d91c652ecfe9/41598_2021_89420_Fig1_HTML.jpg

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