Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway

Bibliographic Details
Title: Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway
Authors: Qing Xie, Zhijie Yang, Xuanmei Huang, Zikang Zhang, Jiangbin Li, Jianhua Ju, Hua Zhang, Junying Ma
Source: Journal of Hematology & Oncology, Vol 12, Iss 1, Pp 1-14 (2019)
Publisher Information: BMC, 2019.
Publication Year: 2019
Collection: LCC:Diseases of the blood and blood-forming organs
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: Ilamycin C, Triple-negative breast cancer, Apoptosis, Invasion, Migration, IL-6, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: Abstract Background Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis, and its treatment remains a challenge due to few targeted medicines and high risk of relapse, metastasis, and drug resistance. Thus, more effective drugs and new regimens for the therapy of TNBC are urgently needed. Ilamycins are a kind of cyclic peptides and produced by Streptomyces atratus and Streptomyces islandicus with effective anti-tuberculosis activity. Ilamycin C is a novel compound isolated from the deep South China Sea-derived Streptomyces atratus SCSIO ZH16 and exhibited a strong cytotoxic activity against several cancers including breast cancer cell line MCF7. However, the cytotoxic activity of Ilamycin C to TNBC cells and a detailed antitumor mechanism have not been reported. Methods CCK-8 assays were used to examine cell viability and cytotoxic activity of Ilamycin C to TNBC, non-TNBC MCF7, and nonmalignant MCF10A cells. EdU assays and flow cytometry were performed to assess cell proliferation and cell apoptosis. Transwell migration and Matrigel invasion assays were utilized to assess the migratory and invading capacity of TNBC cells following the treatment of Ilamycin C. The expressions of proteins were detected by western blot. Results In this study, we found that Ilamycin C has more preferential cytotoxicity in TNBC cells than non-TNBC MCF7 and nonmalignant MCF10A cells. Notably, our studies revealed the mechanism that Ilamycin C can induce Bax/Bcl-2-related caspase-dependent apoptosis and inhibit migration and invasion through MMP2/MMP9/vimentin/fascin in TNBC by suppressing IL-6-induced STAT3 phosphorylation. Conclusions This study provides the first evidence that Ilamycin C has significant implications for the potential as a novel IL-6/STAT3 inhibitor for TNBC treatment in the future.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1756-8722
Relation: http://link.springer.com/article/10.1186/s13045-019-0744-3; https://doaj.org/toc/1756-8722
DOI: 10.1186/s13045-019-0744-3
Access URL: https://doaj.org/article/60ae34078e5b41d2bcfe4a10bd468098
Accession Number: edsdoj.60ae34078e5b41d2bcfe4a10bd468098
Database: Directory of Open Access Journals
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More Details
ISSN:17568722
DOI:10.1186/s13045-019-0744-3
Published in:Journal of Hematology & Oncology
Language:English