New small molecules targeting apoptosis and cell viability in osteosarcoma
| العنوان: | New small molecules targeting apoptosis and cell viability in osteosarcoma |
|---|---|
| المؤلفون: | Harish K. Potukuchi, Kamyar Hadian, Doris Maugg, Michaela Nathrath, Kenji Schorpp, Daniel Baumhoer, Jan Smida, Ina Rothenaigner, Eberhard Korsching |
| المصدر: | PLoS ONE 10:e0129058 (2015) PLoS ONE PLoS ONE, Vol 10, Iss 6, p e0129058 (2015) |
| بيانات النشر: | Public Library Science, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Cell Survival, lcsh:Medicine, Antineoplastic Agents, Apoptosis, Biology, Pharmacology, Caspase 7, Small Molecule Libraries, Structure-Activity Relationship, Cell Line, Tumor, Drug Discovery, medicine, Humans, Doxorubicin, Viability assay, lcsh:Science, Osteoblasts, Multidisciplinary, Caspase 3, lcsh:R, HEK 293 cells, Mesenchymal stem cell, Mesenchymal Stem Cells, Hep G2 Cells, Staurosporine, medicine.disease, ddc, High-Throughput Screening Assays, Gene Expression Regulation, Neoplastic, Cytolysis, HEK293 Cells, Organ Specificity, Hepatocytes, Cancer research, Osteosarcoma, lcsh:Q, Tumor Suppressor Protein p53, Research Article, Signal Transduction, medicine.drug |
| الوصف: | Despite the option of multimodal therapy in the treatment strategies of osteosarcoma (OS), the most common primary malignant bone tumor, the standard therapy has not changed over the last decades and still involves multidrug chemotherapy and radical surgery. Although successfully applied in many patients a large number of patients eventually develop recurrent or metastatic disease in which current therapeutic regimens often lack efficacy. Thus, new therapeutic strategies are urgently needed. In this study, we performed a phenotypic high-throughput screening campaign using a 25,000 small-molecule diversity library to identify new small molecules selectively targeting osteosarcoma cells. We could identify two new small molecules that specifically reduced cell viability in OS cell lines U2OS and HOS, but affected neither hepatocellular carcinoma cell line (HepG2) nor primary human osteoblasts (hOB). In addition, the two compounds induced caspase 3 and 7 activity in the U2OS cell line. Compared to conventional drugs generally used in OS treatment such as doxorubicin, we indeed observed a greater sensitivity of OS cell viability to the newly identified compounds compared to doxorubicin and staurosporine. The p53-negative OS cell line Saos-2 almost completely lacked sensitivity to compound treatment that could indicate a role of p53 in the drug response. Taken together, our data show potential implications for designing more efficient therapies in OS. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::16a18fb4fc312b390a351b3988401bacTest https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=45106Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....16a18fb4fc312b390a351b3988401bac |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |