In silico identification of thiostrepton as an inhibitor of cancer stem cell growth and an enhancer for chemotherapy in non–small-cell lung cancer

Huang, T. H., Wu, A. T. H., Cheng, T. S., Lin, K. T., Lai, C. J., Hsieh, H. W., Chang, P. M. H., Wu, C. W., Huang, C. Y. F., Chen, K. Y. (December 2019) In silico identification of thiostrepton as an inhibitor of cancer stem cell growth and an enhancer for chemotherapy in non–small-cell lung cancer. Journal of Cellular and Molecular Medicine, 23 (12). pp. 8184-8195. ISSN 15821838 (ISSN)

Abstract

Cancer stem cells (CSCs) play an important role in cancer treatment resistance and disease progression. Identifying an effective anti-CSC agent may lead to improved disease control. We used CSC-associated gene signatures to identify drug candidates that may inhibit CSC growth by reversing the CSC gene signature. Thiostrepton, a natural cyclic oligopeptide antibiotic, was the top-ranked candidate. In non–small-cell lung cancer (NSCLC) cells, thiostrepton inhibited CSC growth in vitro and reduced protein expression of cancer stemness markers, including CD133, Nanog and Oct4A. In addition, metastasis-associated Src tyrosine kinase signalling, cell migration and epithelial-to-mesenchymal transition (EMT) were all inhibited by thiostrepton. Mechanistically, thiostrepton treatment led to elevated levels of tumour suppressor miR-98. Thiostrepton combined with gemcitabine synergistically suppressed NSCLC cell growth and induced apoptosis. The inhibition of NSCLC tumours and CSC growth by thiostrepton was also demonstrated in vivo. Our findings indicate that thiostrepton, an established drug identified in silico, is an inhibitor of CSC growth and a potential enhancer of chemotherapy in NSCLC. © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Item Type:	Paper
Additional Information:	J. Cell. Mol. Med.
Uncontrolled Keywords:	cancer stem cell epithelial-to-mesenchymal transition miR-98 non–small-cell lung cancer thiostrepton
Subjects:	diseases & disorders > cancer diseases & disorders diseases & disorders > neoplasms organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell proliferation organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions diseases & disorders > cancer > drugs and therapies > chemotherapy diseases & disorders > cancer > drugs and therapies diseases & disorders > cancer > cancer types > lung cancer organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent organs, tissues, organelles, cell types and functions > tissues types and functions > signal transduction organs, tissues, organelles, cell types and functions > tissues types and functions diseases & disorders > cancer > cancer types
CSHL Authors:	Lin, Kuan-Ting
Depositing User:	Adrian Gomez
Date:	1 December 2019
Date Deposited:	11 Dec 2019 15:55
Last Modified:	02 Feb 2024 15:47
Related URLs:	Publisher PubMed
URI:	https://repository.cshl.edu/id/eprint/38742

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