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...
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doaj-6eb8b062ab2d44d5a8c962c9246bc9be2020-11-25T02:03:04ZengMDPI AGMolecules1420-30492020-04-01251793179310.3390/molecules25081793CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft ModelLi-Yun Fann0Jui-Hu Shih1Jen-Ho Tseng2Hsu-Shan Huang3Sheng-Huang Hsiao4Department of Nursing, Taipei City Hospital, Taipei 10684, TaiwanDepartment of Pharmacy Practice, Tri-Service General Hospital, Taipei 11490, TaiwanDepartment of Neurosurgery, Taipei City Hospital, Taipei 10684, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Neurosurgery, Taipei City Hospital, Taipei 10684, TaiwanAmong 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.https://www.mdpi.com/1420-3049/25/8/1793apoptosisbrain tumorcell arrestchemotherapyDNA damageglioblastoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Li-Yun Fann Jui-Hu Shih Jen-Ho Tseng Hsu-Shan Huang Sheng-Huang Hsiao |
spellingShingle |
Li-Yun Fann Jui-Hu Shih Jen-Ho Tseng Hsu-Shan Huang Sheng-Huang Hsiao CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model Molecules apoptosis brain tumor cell arrest chemotherapy DNA damage glioblastoma |
author_facet |
Li-Yun Fann Jui-Hu Shih Jen-Ho Tseng Hsu-Shan Huang Sheng-Huang Hsiao |
author_sort |
Li-Yun Fann |
title |
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_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_sort |
cc12 induces apoptotic cell death and cell cycle arrest in human glioblastoma cell lines and mouse xenograft model |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2020-04-01 |
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. |
topic |
apoptosis brain tumor cell arrest chemotherapy DNA damage glioblastoma |
url |
https://www.mdpi.com/1420-3049/25/8/1793 |
work_keys_str_mv |
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