Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/52461 |
Resumo: | © Impact Journals, LLC. 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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Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastomaAlsterpaulloneConnectivity mapGroup 3 medulloblastoma; piperlongumine© Impact Journals, LLC. 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.Advances in the molecular biology of medulloblastoma revealed four genetically and clinically distinct subgroups. Group 3 medulloblastomas are characterized by frequent amplifications of the oncogene MYC, a high incidence of metastasis, and poor prognosis despite aggressive therapy. We investigated several potential small molecule inhibitors to target Group 3 medulloblastomas based on gene expression data using an in silico drug screen. The Connectivity Map (C-MAP) analysis identified piperlongumine as the top candidate drug for non-WNT medulloblastomas and the cyclin-dependent kinase (CDK) inhibitor alsterpaullone as the compound predicted to have specific antitumor activity against Group 3 medulloblastomas. To validate our findings we used these inhibitors against established Group 3 medulloblastoma cell lines. The C-MAP predicted drugs reduced cell proliferation in vitro and increased survival in Group 3 medulloblastoma xenografts. Alsterpaullone had the highest efficacy in Group 3 medulloblastoma cells. Genomic profiling of Group 3 medulloblastoma cells treated with alsterpaullone confirmed inhibition of cell cycle-related genes, and down-regulation of MYC. Our results demonstrate the preclinical efficacy of using a targeted therapy approach for Group 3 medulloblastomas. Specifically, we provide rationale for advancing alsterpaullone as a targeted therapy in Group 3 medulloblastoma.This study was supported by the Canadian Cancer Society (Grant #2011-70051), the Pediatric Brain Tumor Foundation of the United States, the Brain Tumour Foundation of Canada, Meagan’s Walk, b.r.a.i.n.child and the Wiley Fund at the Hospital for Sick Children.Impact JournalsRepositório da Universidade de LisboaFaria, ClaudiaAgnihotri, SameerMack, Stephen C.Golbourn, Brian J.Diaz, Roberto J.Olsen, SamanthaBryant, MelissaBebenek, MatthewWang, XinBertrand, Kelsey C.Kushida, MichelleHead, ReneeClark, IanDirks, PeterSmith, Christian A.Taylor, Michael D.Rutka, James T.2022-04-20T16:03:42Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/52461engOncotarget. 2015 Aug 28;6(25):21718-2910.18632/oncotarget.43041949-2553info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:57:41Zoai:repositorio.ul.pt:10451/52461Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:03:33.882976Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma |
| title |
Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma |
| spellingShingle |
Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma Faria, Claudia Alsterpaullone Connectivity map Group 3 medulloblastoma; piperlongumine |
| title_short |
Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma |
| title_full |
Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma |
| title_fullStr |
Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma |
| title_full_unstemmed |
Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma |
| title_sort |
Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma |
| author |
Faria, Claudia |
| author_facet |
Faria, Claudia Agnihotri, Sameer Mack, Stephen C. Golbourn, Brian J. Diaz, Roberto J. Olsen, Samantha Bryant, Melissa Bebenek, Matthew Wang, Xin Bertrand, Kelsey C. Kushida, Michelle Head, Renee Clark, Ian Dirks, Peter Smith, Christian A. Taylor, Michael D. Rutka, James T. |
| author_role |
author |
| author2 |
Agnihotri, Sameer Mack, Stephen C. Golbourn, Brian J. Diaz, Roberto J. Olsen, Samantha Bryant, Melissa Bebenek, Matthew Wang, Xin Bertrand, Kelsey C. Kushida, Michelle Head, Renee Clark, Ian Dirks, Peter Smith, Christian A. Taylor, Michael D. Rutka, James T. |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Faria, Claudia Agnihotri, Sameer Mack, Stephen C. Golbourn, Brian J. Diaz, Roberto J. Olsen, Samantha Bryant, Melissa Bebenek, Matthew Wang, Xin Bertrand, Kelsey C. Kushida, Michelle Head, Renee Clark, Ian Dirks, Peter Smith, Christian A. Taylor, Michael D. Rutka, James T. |
| dc.subject.por.fl_str_mv |
Alsterpaullone Connectivity map Group 3 medulloblastoma; piperlongumine |
| topic |
Alsterpaullone Connectivity map Group 3 medulloblastoma; piperlongumine |
| description |
© Impact Journals, LLC. 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. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z 2022-04-20T16:03:42Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/52461 |
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http://hdl.handle.net/10451/52461 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Oncotarget. 2015 Aug 28;6(25):21718-29 10.18632/oncotarget.4304 1949-2553 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Impact Journals |
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Impact Journals |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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