山楂叶的抗氧化、抗溶血作用及其对顺铂抑制 A549 人肺癌细胞增殖作用的影响。

Anti-Oxidant, Anti-Hemolytic Effects of Crataegus aronia Leaves and Its Anti- Proliferative Effect Enhance Cisplatin Cytotoxicity in A549 Human Lung Cancer Cell Line.

机构信息

Doctoral School of Science and Technology, Research Platform for Environmental Science (PRASE), Faculty of Sciences, Lebanese University, Lebanon.

Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon, Lebanon.

出版信息

Asian Pac J Cancer Prev. 2020 Oct 1;21(10):2993-3003. doi: 10.31557/APJCP.2020.21.10.2993.

DOI:10.31557/APJCP.2020.21.10.2993

PMID:33112559

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7798177/

Abstract

OBJECTIVE

For Arabian traditional medicine, Crataegus aronia syn. Azarolus (L) Bosc. ex DC (Rosaceae) is widely used to treat diabetes, sexual weakness, cardiovascular diseases and cancer. The anti-cancerous and anti-hemolysis effects of the hydroalcoholic extract of this plant have never been investigated before. The present study aims to evaluate the biological activities of the hydroalcoholic extract of Crataegus aronia leaves in combination with cisplatin, one of the most widely employed chemotherapeutics, on A549 human lung cancer cell line.

METHODS

The anti-oxidant and anti-proliferative activities of leaves, fruits, seeds of C. aronia were investigated by DPPH method and MTT assay; respectively. Cell migration activity was investigated by wound healing and by cell aggregation assays. The effect of C. aronia in inducing cell cycle arrest along with activating cell apoptosis was evaluated by flow cytometry and Western blot assays, respectively.

RESULTS

Our results showed that C. aronia leaves (C. aronia L.) had the highest anti-oxidant and anti-proliferative activities. The leaves extract was potent against hemolysis of the human erythrocytes and showed elevated decrease in migration by reducing wound healing migration and by increasing cell aggregation. Finally, C. aronia L. treatment exhibited apoptotic activity on A549 cells by the down-regulation of PARP-1, caspase-3 and Bcl-2 proteins and by increasing the percentage of A549 cells in sub G0 cell cycle. Moreover, the co-treatment of C. aronia L. and cisplatin remarkably sensitised A549 cells to cisplatin.

CONCLUSION

The results suggested that C. aronia L. could be used as a potential treatment against human lung cancer exhibiting minimal side effects on human health.
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摘要

目的

在阿拉伯传统医学中，山茱萸（Crataegus aronia syn. Azarolus）（蔷薇科）被广泛用于治疗糖尿病、性功能减退、心血管疾病和癌症。该植物水醇提取物的抗癌和抗溶血作用以前从未被研究过。本研究旨在评估山茱萸叶水醇提取物与顺铂联合使用对 A549 人肺癌细胞系的生物活性，顺铂是最广泛使用的化疗药物之一。

方法

通过 DPPH 法和 MTT 测定法分别研究了山茱萸叶、果实、种子的抗氧化和抗增殖活性。通过划痕愈合和细胞聚集试验研究了细胞迁移活性。通过流式细胞术和 Western blot 分析分别评估了 C. aronia 诱导细胞周期停滞和激活细胞凋亡的作用。

结果

我们的结果表明，山茱萸叶（C. aronia L.）具有最高的抗氧化和抗增殖活性。该叶提取物对人红细胞溶血具有很强的抑制作用，并通过减少划痕愈合迁移和增加细胞聚集来显著降低迁移。最后，C. aronia L. 处理通过下调 PARP-1、caspase-3 和 Bcl-2 蛋白以及增加 A549 细胞在亚 G0 细胞周期中的比例，对 A549 细胞表现出凋亡活性。此外，C. aronia L. 和顺铂的联合治疗显著增加了 A549 细胞对顺铂的敏感性。