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Bishonokiol A inhibits breast cancer cell invasion and migration by suppressing hypoxia inducible factor-1α.
Journal of Bioenergetics and Biomembranes ( IF 3 ) Pub Date : 2019-05-06 , DOI: 10.1007/s10863-019-09799-3
Hong-Mei Li 1 , Jian Miao 1 , Meilin Zhu 1 , Meijia Gao 1 , Yiqun Dai 1 , Qiang Huo 1 , Tao Ma 1 , Cheng-Zhu Wu 1
Affiliation  

Hypoxia inducible factor-1α (HIF-1α) plays a central role in cell survival, invasion, metastasis and angiogenesis, and also is emerging as an important target in anti-cancer drug discovery. In the present study, bishonokiol A, a dimeric neolignan isolated from Magnolia grandiflora, was identified as a novel HIF-1α inhibitor. We here demonstrated that in a dose-dependent manner, bishonokiol A inhibited metastasis-related cell invasion and migration of cobalt chloride (CoCl2)-induced MCF-7 and MDA-MB-231 cells, associating with the reduction in HIF-1α levels. Transfection of MDA-MB-231 cells with HIF-1α small interfering ribonucleic acid (siRNA) resulted in a reduction in cell invasion and migration. Furthermore, we found that bishonokiol A not only inhibited the synthesis of HIF-1α protein and protein kinase B (AKT-473) phosphorylation without affecting the expression of HIF-1α mRNA or ubiquitination degradation, but also inhibited the expression of matrix metalloproteinase-9 (MMP-9) and promoter activity. Nude mice bearing MDA-MB-231 cells incubation were treated with bishonokiol A and results showed that bishonokiol A exhibited potent antitumor activity and low toxicity. Therefore, we suggest that bishonokiol A may be a potential inhibitor of HIF-1α and effective antitumor agent for breast cancer.

中文翻译:

Bishonokiol A通过抑制缺氧诱导因子1α抑制乳腺癌细胞的侵袭和迁移。

缺氧诱导因子-1α(HIF-1α)在细胞存活,侵袭,转移和血管生成中起着核心作用,并且正在成为抗癌药物发现的重要靶标。在本研究中,比索诺基酚A(一种从木兰木兰中分离出来的二聚体新木脂素)被鉴定为新型HIF-1α抑制剂。我们在这里证明,以剂量依赖的方式,联苯甲酚A抑制了与转移相关的细胞入侵和氯化钴(CoCl2)诱导的MCF-7和MDA-MB-231细胞的迁移,与HIF-1α水平的降低有关。用HIF-1α小干扰核糖核酸(siRNA)转染MDA-MB-231细胞可减少细胞侵袭和迁移。此外,我们发现,泛灵酚A不仅可以抑制HIF-1α蛋白和蛋白激酶B(AKT-473)的磷酸化,而不会影响HIF-1αmRNA的表达或泛素降解,还可以抑制基质金属蛋白酶9(MMP)的表达。 -9)和启动子活性。用厚朴酚A处理裸露的带有MDA-MB-231细胞的裸鼠,结果表明,厚朴酚A表现出强大的抗肿瘤活性和低毒性。因此,我们认为联萘酚酚A可能是HIF-1α的潜在抑制剂,也是乳腺癌的有效抗肿瘤药。用厚朴酚A处理裸露的带有MDA-MB-231细胞的裸鼠,结果表明,厚朴酚A表现出强大的抗肿瘤活性和低毒性。因此,我们认为联萘酚酚A可能是HIF-1α的潜在抑制剂,也是乳腺癌的有效抗肿瘤药。用厚朴酚A处理裸露的带有MDA-MB-231细胞的裸鼠,结果表明,厚朴酚A表现出强大的抗肿瘤活性和低毒性。因此,我们认为联萘酚酚A可能是HIF-1α的潜在抑制剂,也是乳腺癌的有效抗肿瘤药。
更新日期:2019-05-06
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