| Autor: |
Rajesha Rupaimoole, Bohyung Yoon, Wen Cai Zhang, Brian D. Adams, Frank J. Slack |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 23, Iss 2, Pp - (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2020.100878 |
| Popis: |
Summary: MicroRNA-34 (miR-34) is one of the major families of tumor suppressor miRNAs often lost in cancers. Delivery of miR-34a mimics to affected tumors as a therapeutic strategy has been tried in pre-clinical studies and in a phase I clinical trial. One approach to increase efficacy and reduce toxicity is to rationally identify drug combinations with small molecules that synergize with miR-34a. In this study we performed a high-throughput screen of a large panel of small molecules with known biological activity and identified ouabain as a candidate small molecule that synergized with miR-34a in killing lung cancer cells. We elucidated autophagy activation as a key mechanism by which miR-34a and ouabain causes increased cytotoxicity in cells. We posit that this combinatorial approach could reduce the active dose of miR-34a needed in vivo to observe tumor shrinkage and potentiate the development of miR-34a combination therapies in the future. : Biomolecules; Biotechnology; Cancer Subject Areas: Biomolecules, Biotechnology, Cancer |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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