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青蒿素半合成衍生物诱导人乳腺癌MCF-7细胞凋亡:一种与半胱天冬酶相关的机制

Induction of Apoptosis in Human Breast Cancer MCF-7 Cells by a Semi-Synthetic Derivative of Artemisinin: A Caspase-Related Mechanism.

作者信息

Jamalzadeh Leila, Ghafoori Hossein, Aghamaali Mahmoodreza, Sariri Reyhaneh

机构信息

Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran.

出版信息

Iran J Biotechnol. 2017 Sep 27;15(3):157-165. doi: 10.15171/ijb.1567. eCollection 2017.

Abstract

Artesunate has recently been used in some pharmacological preparation to induce tumor cell apoptosis. The drug is a semi-synthetic derivative of artemisinin, traditionally used for its antimalarial. However, up to now, its anticancer mechanism against different types of tumors is not known. The most important purposes of the present research was firstly investigating induction of apoptosis on human breast cancer MCF-7 cells by the drug and, in the second place, introducing its possible mechanism of action. The MTT assay was used to investigate the inhibitory effect of artesunate on growth of breast cancer MCF-7 cells. For this aim, different concentrations of artesunate were used to treat the cells and flow cytometry assay was done followed by annexin V-FITC/PI staining. The activities of caspase-3, -8 and -9 were then determined by relative assay kits. Based on the results from MTT assay, it was found that artesunate could significantly inhibit the growth of MCF-7 cells in a dose- and time-dependent manner. On the other hand, the flow cytometry findings showed that the anti-proliferative activity of artesunate on MCF-7 cells is due to apoptosis. Besides, caspase colorimetric assays revealed a significant rise in cellular levels of the initiators (caspase-8 and -9) and effector (caspase-3) in the cells treated by artesunate. According to our results, it could be concluded that artesunate could inhibit the growth of MCF-7 breast cancer cells through induction of apoptosis by intrinsic and extrinsic caspase-dependent pathways. Therefore, we claim that artesunate could be introduced as a suitable candidate for the treatment of the breast cancer.

摘要

青蒿琥酯最近已被用于一些药理制剂中以诱导肿瘤细胞凋亡。该药物是青蒿素的半合成衍生物,传统上用于抗疟疾。然而,到目前为止,其针对不同类型肿瘤的抗癌机制尚不清楚。本研究的最重要目的首先是研究该药物对人乳腺癌MCF-7细胞凋亡的诱导作用,其次是介绍其可能的作用机制。采用MTT法研究青蒿琥酯对乳腺癌MCF-7细胞生长的抑制作用。为此,使用不同浓度的青蒿琥酯处理细胞,并在进行膜联蛋白V-FITC/PI染色后进行流式细胞术检测。然后通过相关检测试剂盒测定半胱天冬酶-3、-8和-9的活性。基于MTT法的结果,发现青蒿琥酯能以剂量和时间依赖性方式显著抑制MCF-7细胞的生长。另一方面,流式细胞术结果表明,青蒿琥酯对MCF-7细胞的抗增殖活性是由于细胞凋亡。此外,半胱天冬酶比色法检测显示,经青蒿琥酯处理的细胞中起始者(半胱天冬酶-8和-9)和效应者(半胱天冬酶-3)的细胞水平显著升高。根据我们的结果,可以得出结论,青蒿琥酯可通过内在和外在的半胱天冬酶依赖性途径诱导细胞凋亡来抑制MCF-7乳腺癌细胞的生长。因此,我们认为青蒿琥酯可作为治疗乳腺癌的合适候选药物。

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