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)

URL: https://www.scopus.com/inward/record.uri?eid=2-s2....
DOI: 10.1111/jcmm.14689

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 > drugs and therapies > chemotherapy
diseases & disorders > cancer > cancer types > lung cancer
CSHL Authors:
Depositing User: Adrian Gomez
Date: 1 December 2019
Date Deposited: 11 Dec 2019 15:55
Last Modified: 11 Dec 2019 15:55
Related URLs:
URI: https://repository.cshl.edu/id/eprint/38742

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving