Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy
Recent studies have indicated that targeting glutathione-S-transferase (GST) isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.3233/ACP-2011-012 |
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| author | Michela Pasello Maria Cristina Manara Francesca Michelacci Marilù Fanelli Claudia Maria Hattinger Giordano Nicoletti Lorena Landuzzi Pier Luigi Lollini Annamaria Caccuri Piero Picci Katia Scotlandi Massimo Serra |
| author_facet | Michela Pasello Maria Cristina Manara Francesca Michelacci Marilù Fanelli Claudia Maria Hattinger Giordano Nicoletti Lorena Landuzzi Pier Luigi Lollini Annamaria Caccuri Piero Picci Katia Scotlandi Massimo Serra |
| author_sort | Michela Pasello |
| collection | DOAJ |
| description | Recent studies have indicated that targeting glutathione-S-transferase (GST) isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel of 15 drug-sensitive and drug-resistant human osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma cell lines, the efficay of the GST-targeting agent 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) has been assessed and related to GST isoenzymes expression (namely GSTP1, GSTA1, GSTM1, and MGST). NBDHEX showed a relevant in vitro activity on all cell lines, including the drug-resistant ones and those with higher GSTs levels. The in vitro activity of NBDHEX was mostly related to cytostatic effects, with a less evident apoptotic induction. NBDHEX positively interacted with doxorubicin, vincristine, cisplatin but showed antagonistic effects with methotrexate. In vivo studies confirmed the cytostatic efficay of NBDHEX and its positive interaction with vincristine in Ewing's sarcoma cells, and also indicated a positive effect against the metastatisation of osteosarcoma cells. The whole body of evidence found in this study indicated that targeting GSTs in osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma may be an interesting new therapeutic option, which can be considered for patients who are scarcely responsive to conventional regimens. |
| format | Article |
| id | doaj-art-8f625881f78f4c1e9ef28d978c521e8c |
| institution | Kabale University |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-8f625881f78f4c1e9ef28d978c521e8c2025-02-03T06:46:20ZengWileyAnalytical Cellular Pathology2210-71772210-71852011-01-0134313114510.3233/ACP-2011-012Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic StrategyMichela Pasello0Maria Cristina Manara1Francesca Michelacci2Marilù Fanelli3Claudia Maria Hattinger4Giordano Nicoletti5Lorena Landuzzi6Pier Luigi Lollini7Annamaria Caccuri8Piero Picci9Katia Scotlandi10Massimo Serra11Rizzoli Orthopaedic Institute, Laboratory of Experimental Oncology, Bologna, ItalyRizzoli Orthopaedic Institute, Laboratory of Experimental Oncology, Bologna, ItalyRizzoli Orthopaedic Institute, Laboratory of Experimental Oncology, Bologna, ItalyRizzoli Orthopaedic Institute, Laboratory of Experimental Oncology, Bologna, ItalyRizzoli Orthopaedic Institute, Laboratory of Experimental Oncology, Bologna, ItalyRizzoli Orthopaedic Institute, Laboratory of Experimental Oncology, Bologna, ItalyRizzoli Orthopaedic Institute, Laboratory of Experimental Oncology, Bologna, ItalyDepartment of Hematology and Oncological Sciences, University of Bologna, Bologna, ItalyDepartment of Chemical Sciences and Technologies, University of “Tor Vergata”, Rome, ItalyRizzoli Orthopaedic Institute, Laboratory of Experimental Oncology, Bologna, ItalyRizzoli Orthopaedic Institute, Laboratory of Experimental Oncology, Bologna, ItalyRizzoli Orthopaedic Institute, Laboratory of Experimental Oncology, Bologna, ItalyRecent studies have indicated that targeting glutathione-S-transferase (GST) isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel of 15 drug-sensitive and drug-resistant human osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma cell lines, the efficay of the GST-targeting agent 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) has been assessed and related to GST isoenzymes expression (namely GSTP1, GSTA1, GSTM1, and MGST). NBDHEX showed a relevant in vitro activity on all cell lines, including the drug-resistant ones and those with higher GSTs levels. The in vitro activity of NBDHEX was mostly related to cytostatic effects, with a less evident apoptotic induction. NBDHEX positively interacted with doxorubicin, vincristine, cisplatin but showed antagonistic effects with methotrexate. In vivo studies confirmed the cytostatic efficay of NBDHEX and its positive interaction with vincristine in Ewing's sarcoma cells, and also indicated a positive effect against the metastatisation of osteosarcoma cells. The whole body of evidence found in this study indicated that targeting GSTs in osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma may be an interesting new therapeutic option, which can be considered for patients who are scarcely responsive to conventional regimens.http://dx.doi.org/10.3233/ACP-2011-012 |
| spellingShingle | Michela Pasello Maria Cristina Manara Francesca Michelacci Marilù Fanelli Claudia Maria Hattinger Giordano Nicoletti Lorena Landuzzi Pier Luigi Lollini Annamaria Caccuri Piero Picci Katia Scotlandi Massimo Serra Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy Analytical Cellular Pathology |
| title | Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy |
| title_full | Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy |
| title_fullStr | Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy |
| title_full_unstemmed | Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy |
| title_short | Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy |
| title_sort | targeting glutathione s transferase enzymes in musculoskeletal sarcomas a promising therapeutic strategy |
| url | http://dx.doi.org/10.3233/ACP-2011-012 |
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