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Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma
Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697826/ https://www.ncbi.nlm.nih.gov/pubmed/29161257 http://dx.doi.org/10.1371/journal.pone.0178881 |
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author | Oh, Jinsoo Kim, Yongbo Che, Lihua Kim, Jeong Beom Chang, Gyeong Eon Cheong, Eunji Kang, Seok-Gu Ha, Yoon |
author_facet | Oh, Jinsoo Kim, Yongbo Che, Lihua Kim, Jeong Beom Chang, Gyeong Eon Cheong, Eunji Kang, Seok-Gu Ha, Yoon |
author_sort | Oh, Jinsoo |
collection | PubMed |
description | Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator). Here, we show that the combined action of CHIR99021 and forskolin converted malignant glioma into fully differentiated neurons with no malignant characteristics; inhibited the proliferation of malignant glioma; and significantly down-regulated gene ontology and gene expression profiles related to cell division, gliogenesis, and angiogenesis in small molecule–induced neurons. In vivo, the combined action of CHIR99021 and forskolin markedly delayed neurological deficits and significantly reduced the tumor volume. We suggest that reprogramming technology may be a potential treatment strategy replacing the therapeutic paradigm of traditional treatment of malignant glioma, and a combination molecule comprising a GSK3 inhibitor and a cAMP inducer could be the next generation of anticancer drugs. |
format | Online Article Text |
id | pubmed-5697826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56978262017-11-30 Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma Oh, Jinsoo Kim, Yongbo Che, Lihua Kim, Jeong Beom Chang, Gyeong Eon Cheong, Eunji Kang, Seok-Gu Ha, Yoon PLoS One Research Article Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator). Here, we show that the combined action of CHIR99021 and forskolin converted malignant glioma into fully differentiated neurons with no malignant characteristics; inhibited the proliferation of malignant glioma; and significantly down-regulated gene ontology and gene expression profiles related to cell division, gliogenesis, and angiogenesis in small molecule–induced neurons. In vivo, the combined action of CHIR99021 and forskolin markedly delayed neurological deficits and significantly reduced the tumor volume. We suggest that reprogramming technology may be a potential treatment strategy replacing the therapeutic paradigm of traditional treatment of malignant glioma, and a combination molecule comprising a GSK3 inhibitor and a cAMP inducer could be the next generation of anticancer drugs. Public Library of Science 2017-11-21 /pmc/articles/PMC5697826/ /pubmed/29161257 http://dx.doi.org/10.1371/journal.pone.0178881 Text en © 2017 Oh et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Oh, Jinsoo Kim, Yongbo Che, Lihua Kim, Jeong Beom Chang, Gyeong Eon Cheong, Eunji Kang, Seok-Gu Ha, Yoon Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma |
title | Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma |
title_full | Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma |
title_fullStr | Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma |
title_full_unstemmed | Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma |
title_short | Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma |
title_sort | regulation of camp and gsk3 signaling pathways contributes to the neuronal conversion of glioma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697826/ https://www.ncbi.nlm.nih.gov/pubmed/29161257 http://dx.doi.org/10.1371/journal.pone.0178881 |
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