New small molecules targeting apoptosis and cell viability in osteosarcoma.
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 pat...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4454490?pdf=render |
| _version_ | 1818356216162680832 |
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| author | Doris Maugg Ina Rothenaigner Kenji Schorpp Harish Kumar Potukuchi Eberhard Korsching Daniel Baumhoer Kamyar Hadian Jan Smida Michaela Nathrath |
| author_facet | Doris Maugg Ina Rothenaigner Kenji Schorpp Harish Kumar Potukuchi Eberhard Korsching Daniel Baumhoer Kamyar Hadian Jan Smida Michaela Nathrath |
| author_sort | Doris Maugg |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T19:53:41Z |
| format | Article |
| id | doaj.art-21b6f33aaf7e4b599c0bb134fee6d4aa |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T19:53:41Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-21b6f33aaf7e4b599c0bb134fee6d4aa2022-12-21T23:33:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e012905810.1371/journal.pone.0129058New small molecules targeting apoptosis and cell viability in osteosarcoma.Doris MauggIna RothenaignerKenji SchorppHarish Kumar PotukuchiEberhard KorschingDaniel BaumhoerKamyar HadianJan SmidaMichaela NathrathDespite 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.http://europepmc.org/articles/PMC4454490?pdf=render |
| spellingShingle | Doris Maugg Ina Rothenaigner Kenji Schorpp Harish Kumar Potukuchi Eberhard Korsching Daniel Baumhoer Kamyar Hadian Jan Smida Michaela Nathrath New small molecules targeting apoptosis and cell viability in osteosarcoma. PLoS ONE |
| title | New small molecules targeting apoptosis and cell viability in osteosarcoma. |
| title_full | New small molecules targeting apoptosis and cell viability in osteosarcoma. |
| title_fullStr | New small molecules targeting apoptosis and cell viability in osteosarcoma. |
| title_full_unstemmed | New small molecules targeting apoptosis and cell viability in osteosarcoma. |
| title_short | New small molecules targeting apoptosis and cell viability in osteosarcoma. |
| title_sort | new small molecules targeting apoptosis and cell viability in osteosarcoma |
| url | http://europepmc.org/articles/PMC4454490?pdf=render |
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