Diana Marklein, Ulrike Graab, Ivonne Naumann, Tiandong Yan, Rosalie Ridzewski, Frauke Nitzki, Albert Rosenberger, Kai Dittmann, Jürgen Wienands, Leszek Wojnowski, Simone Fulda, Heidi Hahn
- We searched for a drug capable of sensitization of sarcoma cells to doxorubicin (DOX). We report that the dual PI3K/mTOR inhibitor PI103 enhances the efficacy of DOX in several sarcoma cell lines and interacts with DOX in the induction of apoptosis. PI103 decreased the expression of MDR1 and MRP1, which resulted in DOX accumulation. However, the enhancement of DOX-induced apoptosis was unrelated to DOX accumulation. Neither did it involve inhibition of mTOR. Instead, the combination treatment of DOX plus PI103 activated Bax, the mitochondrial apoptosis pathway, and caspase 3. Caspase 3 activation was also observed in xenografts of sarcoma cells in nude mice upon combination of DOX with the specific PI3K inhibitor GDC-0941. Although the increase in apoptosis did not further impact on tumor growth when compared to the efficient growth inhibition by GDC-0941 alone, these findings suggest that inhibition of PI3K may improve DOX-induced proapoptotic effects in sarcoma. Taken together with similar recent studies of neuroblastoma- and glioblastoma-derived cells, PI3K inhibition seems to be a more general option to sensitize tumor cells to anthracyclines.
MetadatenAuthor: | Diana Marklein, Ulrike Graab, Ivonne Naumann, Tiandong Yan, Rosalie Ridzewski, Frauke Nitzki, Albert Rosenberger, Kai Dittmann, Jürgen Wienands, Leszek Wojnowski, Simone FuldaORCiDGND, Heidi Hahn |
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URN: | urn:nbn:de:hebis:30:3-283612 |
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DOI: | https://doi.org/10.1371/journal.pone.0052898 |
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ISSN: | 1932-6203 |
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ISSN: | 1932-6203 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/23300809 |
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Parent Title (English): | PLoS One |
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Publisher: | PLoS |
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Place of publication: | Lawrence, Kan. |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2013/01/21 |
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Date of first Publication: | 2012/12/31 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2013/01/21 |
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Volume: | 7 |
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Issue: | (12): e52898 |
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Page Number: | 12 |
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Note: | Copyright: © 2012 Marklein et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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HeBIS-PPN: | 32183870X |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 3.0 |
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