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CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model
Among central nervous system tumors, glioblastoma (GBM) is the most common and the most malignant type. Even under current standard treatments, the overall survival rate is still low and the recurrence rate is high. Therefore, developing novel and effective therapy is urgently needed. CC12, a synthe...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221762/ https://www.ncbi.nlm.nih.gov/pubmed/32295275 http://dx.doi.org/10.3390/molecules25081793 |
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author | Fann, Li-Yun Shih, Jui-Hu Tseng, Jen-Ho Huang, Hsu-Shan Hsiao, Sheng-Huang |
author_facet | Fann, Li-Yun Shih, Jui-Hu Tseng, Jen-Ho Huang, Hsu-Shan Hsiao, Sheng-Huang |
author_sort | Fann, Li-Yun |
collection | PubMed |
description | Among central nervous system tumors, glioblastoma (GBM) is the most common and the most malignant type. Even under current standard treatments, the overall survival rate is still low and the recurrence rate is high. Therefore, developing novel and effective therapy is urgently needed. CC12, a synthesized small molecule, was evaluated for the potential anti-GBM effects in two GBM cell lines, U87MG and U118MG. The observations of cell morphology, MTT assay, flow cytometry-based apoptosis after CC12 treatment, were conducted. Western blot was performed for the investigation of the apoptotic mechanism. Positron emission tomography scan analysis and bioluminescent imaging assay using a mouse xenograft model were performed for the effect of CC12 in vivo. After treated by 10 μM CC12 for 24 h, both U118MG and U87MG cells showed tumor cell death. MTT assay results showed that the survival rates decreased when the CC12 concentrations or the treatment periods increased. Ki-67 expression and flow cytometry results indicated that the proliferation was inhibited in GBM cells, and G1 phase arrest was shown. The results of 7-AAD, Br-dUTP, and JC-1 staining all showed the apoptosis of GBM cells after CC12 treatment. Increased γH2AX, caspase-3, and poly (ADP-ribose) polymerase (PARP) levels meant the DNA damage, and increased Bcl2 family proteins after CC12 treatment indicated the intrinsic apoptotic pathway was involved in CC12 induced apoptosis. Furthermore, CC12 can induce the decrease of tumor prognostic marker DcR3. In vivo experiment results showed the effect of CC12 on tumor size reduction of CC12. In addition, the ability to cross the brain–blood barrier of CC12 was also confirmed. CC12 may have anti-tumor ability through the regulation of cell cycle and apoptosis in vitro and in vivo. |
format | Online Article Text |
id | pubmed-7221762 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72217622020-05-21 CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model Fann, Li-Yun Shih, Jui-Hu Tseng, Jen-Ho Huang, Hsu-Shan Hsiao, Sheng-Huang Molecules Article Among central nervous system tumors, glioblastoma (GBM) is the most common and the most malignant type. Even under current standard treatments, the overall survival rate is still low and the recurrence rate is high. Therefore, developing novel and effective therapy is urgently needed. CC12, a synthesized small molecule, was evaluated for the potential anti-GBM effects in two GBM cell lines, U87MG and U118MG. The observations of cell morphology, MTT assay, flow cytometry-based apoptosis after CC12 treatment, were conducted. Western blot was performed for the investigation of the apoptotic mechanism. Positron emission tomography scan analysis and bioluminescent imaging assay using a mouse xenograft model were performed for the effect of CC12 in vivo. After treated by 10 μM CC12 for 24 h, both U118MG and U87MG cells showed tumor cell death. MTT assay results showed that the survival rates decreased when the CC12 concentrations or the treatment periods increased. Ki-67 expression and flow cytometry results indicated that the proliferation was inhibited in GBM cells, and G1 phase arrest was shown. The results of 7-AAD, Br-dUTP, and JC-1 staining all showed the apoptosis of GBM cells after CC12 treatment. Increased γH2AX, caspase-3, and poly (ADP-ribose) polymerase (PARP) levels meant the DNA damage, and increased Bcl2 family proteins after CC12 treatment indicated the intrinsic apoptotic pathway was involved in CC12 induced apoptosis. Furthermore, CC12 can induce the decrease of tumor prognostic marker DcR3. In vivo experiment results showed the effect of CC12 on tumor size reduction of CC12. In addition, the ability to cross the brain–blood barrier of CC12 was also confirmed. CC12 may have anti-tumor ability through the regulation of cell cycle and apoptosis in vitro and in vivo. MDPI 2020-04-14 /pmc/articles/PMC7221762/ /pubmed/32295275 http://dx.doi.org/10.3390/molecules25081793 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fann, Li-Yun Shih, Jui-Hu Tseng, Jen-Ho Huang, Hsu-Shan Hsiao, Sheng-Huang CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model |
title | CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model |
title_full | CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model |
title_fullStr | CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model |
title_full_unstemmed | CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model |
title_short | CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model |
title_sort | cc12 induces apoptotic cell death and cell cycle arrest in human glioblastoma cell lines and mouse xenograft model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221762/ https://www.ncbi.nlm.nih.gov/pubmed/32295275 http://dx.doi.org/10.3390/molecules25081793 |
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