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Actinomycin V Inhibits Migration and Invasion via Suppressing Snail/Slug-Mediated Epithelial-Mesenchymal Transition Progression in Human Breast Cancer MDA-MB-231 Cells In Vitro

1
School of Ocean, Shandong University, Weihai 264209, China
2
School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
3
The Key Laboratory of Chemistry for Natural Product of Guizhou Province, Chinese Academy of Science, Guiyang 550002, China
*
Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(5), 305; https://doi.org/10.3390/md17050305
Received: 23 April 2019 / Revised: 22 May 2019 / Accepted: 22 May 2019 / Published: 24 May 2019
(This article belongs to the Collection Marine Compounds and Cancer)
Actinomycin V, an analog of actinomycin D produced by the marine-derived actinomycete Streptomyces sp., possessing a 4-ketoproline instead of a 4-proline in actinomycin D. In this study, the involvement of snail/slug-mediated epithelial-mesenchymal transition (EMT) in the anti-migration and -invasion actions of actinomycin V was investigated in human breast cancer MDA-MB-231 cells in vitro. Cell proliferation effect was evaluated by 3-(4,5-Dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. Wound-healing and Transwell assay were performed to investigate the anti-migration and -invasion effects of actinomycin V. Western blotting was used to detect the expression levels of E-cadherin, N-cadherin, vimentin, snail, slug, zinc finger E-box binding homeobox 1 (ZEB1), and twist proteins and the mRNA levels were detected by rt-PCR. Actinomycin V showed stronger cytotoxic activity than that of actinomycin D. Actinomycin V up-regulated both of the protein and mRNA expression levels of E-cadherin and down-regulated that of N-cadherin and vimentin in the same cells. In this connection, actinomycin V decreased the snail and slug protein expression, and consequently inhibited cells EMT procession. Our results suggest that actinomycin V inhibits EMT-mediated migration and invasion via decreasing snail and slug expression, which exhibits therapeutic potential for the treatment of breast cancer and further toxicity investigation in vivo is needed. View Full-Text
Keywords: breast cancer; actinomycin; EMT; migration; invasion breast cancer; actinomycin; EMT; migration; invasion
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Lin, S.; Zhang, C.; Liu, F.; Ma, J.; Jia, F.; Han, Z.; Xie, W.; Li, X. Actinomycin V Inhibits Migration and Invasion via Suppressing Snail/Slug-Mediated Epithelial-Mesenchymal Transition Progression in Human Breast Cancer MDA-MB-231 Cells In Vitro. Mar. Drugs 2019, 17, 305.

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