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Open AccessArticle

CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model

1
Department of Nursing, Taipei City Hospital, Taipei 10684, Taiwan
2
Department of Biology and Anatomy, National Defense Medical Center, Taipei 11490, Taiwan
3
Department of Pharmacy Practice, Tri-Service General Hospital, Taipei 11490, Taiwan
4
School of Pharmacy, National Defense Medical Center, Taipei 10684, Taiwan
5
Department of Neurosurgery, Taipei City Hospital, Taipei 10684, Taiwan
6
Graduate Institute for Cancer Biology & Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11064, Taiwan
*
Authors to whom correspondence should be addressed.
Molecules 2020, 25(8), 1793; https://doi.org/10.3390/molecules25081793
Received: 20 March 2020 / Revised: 6 April 2020 / Accepted: 7 April 2020 / Published: 14 April 2020
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. View Full-Text
Keywords: apoptosis; brain tumor; cell arrest; chemotherapy; DNA damage; glioblastoma apoptosis; brain tumor; cell arrest; chemotherapy; DNA damage; glioblastoma
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MDPI and ACS Style

Fann, L.-Y.; Shih, J.-H.; Tseng, J.-H.; Huang, H.-S.; Hsiao, S.-H. CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model. Molecules 2020, 25, 1793.

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