Assessment of the chemosensitizing activity of TAT-RasGAP317-326 in childhood cancers.
Although current anti-cancer protocols are reasonably effective, treatment-associated long-term side effects, induced by lack of specificity of the anti-cancer procedures, remain a challenging problem in pediatric oncology. TAT-RasGAP317-326 is a RasGAP-derived cell-permeable peptide that acts as a...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4380404?pdf=render |
| _version_ | 1818265406031265792 |
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| author | Nadja Chevalier Nicole Gross Christian Widmann |
| author_facet | Nadja Chevalier Nicole Gross Christian Widmann |
| author_sort | Nadja Chevalier |
| collection | DOAJ |
| description | Although current anti-cancer protocols are reasonably effective, treatment-associated long-term side effects, induced by lack of specificity of the anti-cancer procedures, remain a challenging problem in pediatric oncology. TAT-RasGAP317-326 is a RasGAP-derived cell-permeable peptide that acts as a sensitizer to various anti-cancer treatments in adult tumor cells. In the present study, we assessed the effect of TAT-RasGAP317-326 in several childhood cancer cell lines. The RasGAP-derived peptide-induced cell death was analyzed in several neuroblastoma, Ewing sarcoma and leukemia cell lines (as well as in normal lymphocytes). Cell death was evaluated using flow cytometry methods in the absence or in the presence of the peptide in combination with various genotoxins used in the clinics (4-hydroperoxycyclophosphamide, etoposide, vincristine and doxorubicin). All tested pediatric tumors, in response to at least one genotoxin, were sensitized by TAT-RasGAP317-326. The RasGAP-derived peptide did not increase cell death of normal lymphocytes, alone or in combination with the majority of the tested chemotherapies. Consequently, TAT-RasGAP317-326 may benefit children with tumors by increasing the efficacy of anti-cancer therapies notably by allowing reductions in anti-cancer drug dosage and the associated drug-induced side effects. |
| first_indexed | 2024-12-12T19:50:18Z |
| format | Article |
| id | doaj.art-2adf2173abf34a36a46edce49cbdcbfa |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T19:50:18Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2adf2173abf34a36a46edce49cbdcbfa2022-12-22T00:13:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012048710.1371/journal.pone.0120487Assessment of the chemosensitizing activity of TAT-RasGAP317-326 in childhood cancers.Nadja ChevalierNicole GrossChristian WidmannAlthough current anti-cancer protocols are reasonably effective, treatment-associated long-term side effects, induced by lack of specificity of the anti-cancer procedures, remain a challenging problem in pediatric oncology. TAT-RasGAP317-326 is a RasGAP-derived cell-permeable peptide that acts as a sensitizer to various anti-cancer treatments in adult tumor cells. In the present study, we assessed the effect of TAT-RasGAP317-326 in several childhood cancer cell lines. The RasGAP-derived peptide-induced cell death was analyzed in several neuroblastoma, Ewing sarcoma and leukemia cell lines (as well as in normal lymphocytes). Cell death was evaluated using flow cytometry methods in the absence or in the presence of the peptide in combination with various genotoxins used in the clinics (4-hydroperoxycyclophosphamide, etoposide, vincristine and doxorubicin). All tested pediatric tumors, in response to at least one genotoxin, were sensitized by TAT-RasGAP317-326. The RasGAP-derived peptide did not increase cell death of normal lymphocytes, alone or in combination with the majority of the tested chemotherapies. Consequently, TAT-RasGAP317-326 may benefit children with tumors by increasing the efficacy of anti-cancer therapies notably by allowing reductions in anti-cancer drug dosage and the associated drug-induced side effects.http://europepmc.org/articles/PMC4380404?pdf=render |
| spellingShingle | Nadja Chevalier Nicole Gross Christian Widmann Assessment of the chemosensitizing activity of TAT-RasGAP317-326 in childhood cancers. PLoS ONE |
| title | Assessment of the chemosensitizing activity of TAT-RasGAP317-326 in childhood cancers. |
| title_full | Assessment of the chemosensitizing activity of TAT-RasGAP317-326 in childhood cancers. |
| title_fullStr | Assessment of the chemosensitizing activity of TAT-RasGAP317-326 in childhood cancers. |
| title_full_unstemmed | Assessment of the chemosensitizing activity of TAT-RasGAP317-326 in childhood cancers. |
| title_short | Assessment of the chemosensitizing activity of TAT-RasGAP317-326 in childhood cancers. |
| title_sort | assessment of the chemosensitizing activity of tat rasgap317 326 in childhood cancers |
| url | http://europepmc.org/articles/PMC4380404?pdf=render |
| work_keys_str_mv | AT nadjachevalier assessmentofthechemosensitizingactivityoftatrasgap317326inchildhoodcancers AT nicolegross assessmentofthechemosensitizingactivityoftatrasgap317326inchildhoodcancers AT christianwidmann assessmentofthechemosensitizingactivityoftatrasgap317326inchildhoodcancers |