11PS04 is a new chemical entity identified by microRNA-based biosensing with promising therapeutic potential against cancer stem cells
| Autor: | Rebeca M. Torrente-Rodríguez, Virginia Albiñana, Luisa María Botella, Francisco Sánchez-Sancho, Rosario Granados, Susana Campuzano, Tania Aguado, Angel Cuesta, José-María Sánchez-Puelles, Jose A. Garcia-Sanz, José M. Pingarrón, Silvia Santamaría, José A. Romero-Revilla |
|---|---|
| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Campuzano, Susana [0000-0002-9928-6613], Albiñana, Virginia [0000-0001-9443-1626], Botella, Luisa María [0000-0002-6310-2245], Santamaría, S. [0000-0003-2100-2657], García-Sanz, José A. [0000-0002-1153-6025], Pingarrón, José Manuel [0000-0003-2271-1383 ], Sánchez-Sancho, Francisco [0000-0003-4634-8283], Sánchez-Puelles, José María [0000-0002-4283-4885], Campuzano, Susana, Albiñana, Virginia, Botella, Luisa María, Santamaría, S., García-Sanz, José A., Pingarrón, José Manuel, Sánchez-Sancho, Francisco, Sánchez-Puelles, José María |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Phenotypic screening Carcinogenesis Cell Survival lcsh:Medicine Antineoplastic Agents Biosensing Techniques Computational biology Article Mice 03 medical and health sciences 3D cell culture Mammary Glands Animal 0302 clinical medicine Breast cancer Cancer stem cell Cell Line Tumor Spheroids Cellular New chemical entity microRNA Temozolomide Animals Medicine lcsh:Science Oxazoles Cell Proliferation Multidisciplinary Molecular medicine Drug discovery business.industry Magnetic Phenomena lcsh:R Reproducibility of Results Cancer Glioma medicine.disease Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Neoplastic Stem Cells lcsh:Q Female Classical pharmacology business 030217 neurology & neurosurgery |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) |
| Popis: | 13 p.-5 fig-1 tab. Phenotypic drug discovery must take advantage of the large amount of clinical data currently available. In this sense, the impact of microRNAs (miRs) on human disease and clinical therapeutic responses is becoming increasingly well documented. Accordingly, it might be possible to use miR-based signatures as phenotypic read-outs of pathological status, for example in cancer. Here, we propose to use the information accumulating regarding the biology of miRs from clinical research in the preclinical arena, adapting it to the use of miR biosensors in the earliest steps of drug screening. Thus, we have used an amperometric dual magnetosensor capable of monitoring a miR-21/miR-205 signature to screen for new drugs that restore these miRs to non-tumorigenic levels in cell models of breast cancer and glioblastoma. In this way we have been able to identify a new chemical entity, 11PS04 ((3aR,7aS)-2-(3-propoxyphenyl)-7,7a-dihydro-3aH-pyrano[3,4-d]oxazol-6(4H)-one), the therapeutic potential of which was suggested in mechanistic assays of disease models, including 3D cell culture (oncospheres) and xenografts. These assays highlighted the potential of this compound to attack cancer stem cells, reducing the growth of breast and glioblastoma tumors in vivo. These data demonstrate the enhanced chain of translatability of this strategy, opening up new perspectives for drug-discovery pipelines and highlighting the potential of miR-based electro-analytical sensors as efficient tools in modern drug discovery. This work was supported by grants CTQ2014-52213-R, CTQ2015-64402-C2-1-R and CTQ2015-64402-C2-2-R (Spanish Ministry of Economy and Competitiveness, MINECO), CM S2011/BMED-2353 (Comunidad de Madrid), and FEDER Funds. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|