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

Tse-Hung Huang, Alexander T H Wu, Tai-Shan Cheng, Kuan-Ting Lin, Chia-Jou Lai, Hao-Wen Hsieh, Peter Mu-Hsin Chang, Cheng-Wen Wu, Chi-Ying F Huang, Kuan-Yu Chen

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
JournalJournal of Cellular and Molecular Medicine
DOIs
Publication statusE-pub ahead of print - Oct 22 2019

    Fingerprint

Cite this