南京大学学报(自然科学版) ›› 2021, Vol. 57 ›› Issue (2): 334–343.doi: 10.13232/j.cnki.jnju.2021.02.019

• • 上一篇    

Antimycin类天然产物抗三阴性乳腺癌细胞MDA⁃MB⁃231作用机制初步研究

郭怡1, 姜成燕1, 焦瑞华2(), 蒋爱芹1()   

  1. 1.江苏省医学分子技术重点实验室，转化医学中心，南京大学医学院，南京，210008
    2.南京大学医药生物技术国家重点实验室，南京大学生命科学学院，南京，210023
  • 收稿日期:2021-01-19 出版日期:2021-03-30 发布日期:2021-03-23
  • 通讯作者: 焦瑞华,蒋爱芹 E-mail:rhjiao@nju.edu.cn
  • 作者简介:E⁃mail：rhjiao@nju.edu.cn，jianaq@nju.edu.cn
  • 基金资助:
    国家自然科学基金(81301943);南京大学双创示范基地重点项目(2017)

The inhibitory effects of Antimycin on triple negative breast cancer cell MDA⁃MB⁃231

Yi Guo1, Chengyan Jiang1, Ruihua Jiao2(), Aiqin Jiang1()   

  1. 1.Center of Translational Medicine，Jiangsu Key Laboratory of Molecular Medicine，Nanjing University Medical School，Nanjing University，Nanjing, 210008，China
    2.State Key Laboratory of Pharmaceutical Biotechnology，Institute of Functional Bimolecular，School of Life Sciences，Nanjing University，Nanjing, 210023，China
  • Received:2021-01-19 Online:2021-03-30 Published:2021-03-23
  • Contact: Ruihua Jiao,Aiqin Jiang E-mail:rhjiao@nju.edu.cn

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摘要：

研究Antimycin类天然产物对三阴性乳腺癌细胞MDA?MB?231特异性生长抑制和杀伤作用.三种结构类似的天然产物Antimycin?1，?2和?3对MDA?MB?231细胞生长都有很强的抑制作用，其IC50分别为1.34±0.07，160±20和180±50 nmol·L-1，Antimycin?1活性是Antimycin?2和Antimycin?3的一百多倍.10 nmol·L-1的Antimycin?1就可有效抑制MDA?MB?231细胞增殖，药物处理细胞24和48 h后的抑制率分别达到约80%和90%.显微镜下可以观察到，10和100 nmol·L?1的Antimycin?1都不同程度地杀伤MDA?MB?231细胞，1000 nmol·L-1的Antimycin?1甚至使细胞几乎消溶，只留下突起的核和胞质残骸.而同样浓度药物造成的乳腺正常细胞MCF?10A和结肠癌细胞HCT116形态的改变不明显.1和5 nmol·L-1的Antimycin?1对细胞集落抑制率分别达到52%和95%.20和50 nmol·L-1的Antimycin?1也明显改变MDA?MB?231细胞核形态，核呈畸形，皱缩严重，核膜破损.5，10和100 nmol·L-1的Antimycin?1处理MDA?MB?231细胞12，24和48 h引发细胞凋亡和坏死数量增加，并呈现时间和剂量依赖性.5，10和20 nmol·L-1的Antimycin?1处理MDA?MB?231细胞6，12和24 h后，没有观察到对细胞周期时相的明显影响.20 nmol·L-1的Antimycin?1处理MDA?MB?231细胞12，16，20和24 h后，引起胞内活性氧（reactive oxygen species，ROS）水平随处理时间延长呈逐渐下降趋势.以上结果证明，纳摩尔级的Antimycin?1能有效抑制和杀伤三阴性乳腺癌MDA?MB?231细胞.

关键词: Antimycin, MDA?MB?231, MCF?10A, IC50

Abstract:

In current work，the inhibitory and killing effects of Antimycin on Triple Negative Breast Cancer cell MDA?MB?231 were studied. Three natural products with similar structure，Antimycin?1，?2 and ?3，had strong inhibitory effects on the growth of MDA?MB?231 cells. And the IC50 were 1.34±0.07，160±20 and 180±50 nmol·L-1，respectively. The activity of Antimycin?1 was about one hundred times higher than that of Antimycin?2 and Antimycin?3. 10 nmol·L-1 Antimycin?1 could effectively inhibit the proliferation of MDA?MB?231 cells and the inhibition rates were about 80% and 90% after 24 h and 48 h treatment. The morphology of MDA?MB?231 cells were observed after treated with different concentrations of Antimycin?1. 10 and 100 nmol·L-1 of Antimycin?1 killed most MDA?MB?231 cells. 1000 nmol·L-1 concentration of Antimycin?1 made the cells almost dissolve，leaving the nucleus and cytoplasmic debris. However，the morphology of MCF?10A cells and HCT116 cells were not significantly changed at the same concentrations of drugs. 20 and 50 nmol·L-1 Antimycin?1 also significantly changed the nuclear morphology of MDA?MB?231 cells. The nucleus showed deformity，severe shrinkage and nuclear membrane damage. Treated with antimycin?1 at 5，10，100 nmol·L-1 concentrations for 12，24 and 48 h，the numbers of apoptosis and necrosis of MDA?MB?231 cells increased in a time and dose?dependent manner. After treatment with Antimycin?1 at concentrations of 5，10 and 20 nmol·L-1 for 6，12 and 24 h，no significant effects on cell cycle phase of MDA?MB?231 were observed. And the level of ROS (reactive oxygen species) in MDA?MB?231 cells decreased gradually with the prolongation of treatment time，after MDA?MB?231 cells were treated with 20 nmol·L-1 Antimycin?1. These results showed that Antimycin?1 at nanomolar concentration could effectively inhibit and kill MDA?MB?231 cells.

Key words: Antimycin, MDA?MB?231, MCF?10A, IC50

中图分类号: 

  • R979.1+4

图1

Antimycin类药物对肿瘤细胞生长抑制作用"

图2

Antimycin?1对MDA?MB?231细胞的抑制及杀伤作用"

图3

Antimycin?1对MDA?MB?231细胞核的损伤作用"

图4

Antimycin?1对MDA?MB?231细胞凋亡的影响"

图5

Antimycin?1对MDA?MB?231细胞周期时相的影响"

图6

Antimycin?1对MDA?MB?231细胞产生ROS的影响"

1 Liu J，Zhu X J，Kim S J，et al. Antimycin?type depsipeptides：discovery，biosynthesis，chemical synthesis，and bioactivities. Natural Product Reports，2016，33(10)：1146-1165.
2 Shiomi K，Hatae K，Hatano H，et al. A new antibiotic，antimycin A9，produced by Streptomyces sp. K01?0031. The Journal of Antibiotics，2005，58(1)：74-78.
3 Hosotani N，Kumagai K，Nakagawa H，et al. Antimycins A10~A16，seven new antimycin antibiotics produced by Streptomyces spp. SPA?10191 and SPA?8893. The Journal of Antibiotics，2005，58(7)：460-467.
4 Yan L L，Han N N，Zhang Y Q，et al. Antimycin A18 produced by an endophytic Streptomyces albidoflavus isolated from a mangrove plant. The Journal of Antibiotics，2010，63(5)：259-261.
5 Hayashi K I，Nozaki H. Kitamycins，new antimycin antibiotics produced by Streptomyces sp. The Journal of Antibiotics，1999，52(3)：325-328.
6 Pham N A，Robinson B H，Hedley D W. Simultaneous detection of mitochondrial respiratory chain activity and reactive oxygen in digitonin?permeabilized cells using flow cytometry. Cytometry，2000，41(4)：245-251.
7 Woo H P,Bo R Y. Antimycin A induces death of the human pulmonary fibroblast cells via ROS increase and GSH depletion. International Journal of Oncology,2016,48(2),813-820.
8 Tzung S P，Kim K M，Basa?ez G，et al. Antimycin A mimics a cell?death?inducing Bcl?2 homology domain 3. Nature Cell Biology，2001，3(2)：183-191.
9 Kozone I，Ueda J Y，Takagi M，et al. JBIR?52，a new antimycin?like compound，from Streptomyces sp. ML55. The Journal of Antibiotics，2009，62(10)：593-595.
10 Yeh C T，Su C L，Huang C Y F，et al. A preclinical evaluation of antimycin a as a potential antilung cancer stem cell agent. Evidence?based Complementary and Alternative Medicine，2013，2013：910451.
11 Maeda M，Hasebe Y，Egawa K，et al. Inhibition of angiogenesis and HIF?1α activity by antimycin A1. Biological & Pharmaceutical Bulletin，2006，29(7)：1344-1348.
12 Semenza G L. Targeting HIF?1 for cancer therapy. Nature Reviews Cancer，2003，3(10)：721-732.
13 Salim A A，Cho K J，Tan L X，et al. Rare Streptomyces N?formyl amino?salicylamides inhibit oncogenic K?Ras. Organic Letters，2014，16(19)：5036-5039.
14 Han W，Jung E M，Cho J，et al. DNA copy number alterations and expression of relevant genes in triple?negative breast cancer. Genes，Chromosomes and Cancer，2008，47(6)：490-499.
15 Akiyama F，Iwase H. Triple negative breast cancer：clinicopathological characteristics and treatment strategies. Breast Cancer，2009，16(4)：252-253.
16 Diana A，Carlino F，Franzese E，et al. Early triple negative breast cancer：conventional treatment and emerging therapeutic landscapes. Cancers，2020，12(4)：819-833.
17 Jhan J R，Andrechek E R. Triple?negative breast cancer and the potential for targeted therapy. Pharmacogenomics，2017，18(17)：1595-1609.
18 Yu K J，Rohr J，Liu Y，et al. Progress in triple negative breast carcinoma pathophysiology：potential therapeutic targets. Pathology ? Research and Practice，2020，216(4)：152874.
19 Dent R，Trudeau M，Pritchard K I，et al. Triple?negative breast cancer：clinical features and patterns of recurrence. Clinical Cancer Research，2007，13(15Pt 1)：4429-4434.
20 Bianchini G，Balko J M，Mayer I A，et al. Triple?negative breast cancer：challenges and opportunities of a heterogeneous disease. Nature Reviews Clinical Oncology，2016，13(11)：674-690.
21 Camorani S，Fedele M，Zannetti A，et al. TNBC challenge：oligonucleotide aptamers for new imaging and therapy modalities. Pharmaceuticals，2018，11(4)：123-143.
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