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氧化苦参碱通过线粒体介导的凋亡促进人乳腺癌细胞的S期阻滞并抑制其体外增殖。

Oxymatrine Promotes S-Phase Arrest and Inhibits Cell Proliferation of Human Breast Cancer Cells in Vitro through Mitochondria-Mediated Apoptosis.

作者信息

Wu Jie, Cai Yan, Li Maolan, Zhang Yijian, Li Huaifeng, Tan Zhujun

机构信息

MOE Key Laboratory of Hydrodynamics and School of Naval Architecture, Ocean and Civil Engineering, Shanghai Jiao Tong University.

School of Biological Science and Medical Engineering, Southeast University.

出版信息

Biol Pharm Bull. 2017;40(8):1232-1239. doi: 10.1248/bpb.b17-00010.

DOI:10.1248/bpb.b17-00010
PMID:28769005
Abstract

Breast cancer is one of the most lethal malignancies in the world. Oxymatrine is the major effective and toxic alkaloid component which is derived from the root of Sophora flavescens AIT, a traditional Chinese medicine which is widely distributed in Asia and the Pacific Islands. In the current research study, we investigated the effects and mechanisms of action of oxymatrine on breast cancer cells. We demonstrated that the viability and single cell proliferation capability of MCF-7 and MDA-MB-231, two breast cancer cell lines which are widely used in in vitro study, were significantly suppressed in a time- and concentration-dependent manner. Furthermore, the cell cycle of breast cancer cells treated with oxymatrine was arrested at the S-phase of the cell cycle. Oxymatrine also triggered apoptosis in breast cancer cells by modulating apoptosis-related proteins, such as cleaved Caspase-3, cleaved Caspase-9 and poly(ADP-ribose)polymerase (PARP). The remarkable reduction in the ratio of Bcl-2/Bax was also observed in oxymatrine treated breast cancer cells. In conclusion, our research demonstrated that oxymatrine plays a critical role in suppressing carcinogenesis of breast cancer cells through cell cycle arrest and induction of mitochondria-mediated apoptosis, which suggests a promising application of this drug in breast cancer therapy.

摘要

乳腺癌是全球最致命的恶性肿瘤之一。氧化苦参碱是从苦参(一种广泛分布于亚洲和太平洋岛屿的传统中药)根部提取的主要有效且有毒的生物碱成分。在当前的研究中,我们探究了氧化苦参碱对乳腺癌细胞的作用及其机制。我们证明,在体外研究中广泛使用的两种乳腺癌细胞系MCF-7和MDA-MB-231的活力和单细胞增殖能力,以时间和浓度依赖性方式受到显著抑制。此外,用氧化苦参碱处理的乳腺癌细胞的细胞周期停滞在细胞周期的S期。氧化苦参碱还通过调节凋亡相关蛋白,如裂解的半胱天冬酶-3、裂解的半胱天冬酶-9和聚(ADP-核糖)聚合酶(PARP),触发乳腺癌细胞凋亡。在用氧化苦参碱处理的乳腺癌细胞中还观察到Bcl-2/Bax比值显著降低。总之,我们的研究表明,氧化苦参碱通过细胞周期停滞和诱导线粒体介导的凋亡在抑制乳腺癌细胞癌变中起关键作用,这表明该药物在乳腺癌治疗中有广阔的应用前景。

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