Experimental study of a novel tumstatin on C6 brain glioma in vitro

Zhang,Pengguo; Zhou,Qingwei; Tian,Lin; Zhou,Xiangyu; Zhou,Yue; Chen,Jiajun

doi:10.3892/ol.2017.6507

Experimental study of a novel tumstatin on C6 brain glioma in vitro

Authors:
- Pengguo Zhang
- Qingwei Zhou
- Lin Tian
- Xiangyu Zhou
- Yue Zhou
- Jiajun Chen
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Affiliations: Department of Radiology, Jilin University Second Hospital, Changchun, Jilin 130022, P.R. China, Department of Biology and Medical Engineering, School of Regenerative Medicine, Jilin University, Changchun, Jilin 130022, P.R. China, Department of Biology and Medical Engineering, School of Pharmacy, Jilin University, Changchun, Jilin 130022, P.R. China, Department of Neurology, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130022, P.R. China, Department of Biological Preparation, School of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China
Published online on: June 30, 2017 https://doi.org/10.3892/ol.2017.6507
Pages: 2845-2851
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

To investigate the effect of a novel tumstatin on C6 brain glioma cells, the MTT method was used to detect C6 glioma cell proliferation activity at different time periods (12, 48 and 72 h). Cell cycle distribution and apoptosis rate were detected by flow cytometry, and the acridine orange/ethidium bromide staining method was used to detect apoptosis and mitochondrial membrane potential by fluorescence microscopy. Novel tumstatin had an evident inhibitory effect on C6 glioma cells, and the most notable impact emerged after 48 h. The following were observed under the fluorescence microscope: Characteristic morphological changes of cell apoptosis were typically observed in the novel tumstatin (2,000 µg/ml) group; mitochondrial membrane potential decreased significantly (P<0.05); the cells in the G0/G1 phase significantly increased (P<0.05); and the number of cells in the S phase was reduced. There was an increase in cell apoptosis rate in the novel tumstatin (2,000 µg/ml) group compared with the novel tumstatin (1,000 µg/ml) group and the Mock group, and the data were statistically significant (P<0.05). Novel tumstatin may reduce the mitochondrial membrane potential, inducing cell apoptosis, and thereby exerting antitumor activity.

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1	Auffinger B, Spencer D, Pytel P, Ahmed AU and Lesniak MS: The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence. Expert Rev Neurother. 15:741–752. 2015. View Article : Google Scholar : PubMed/NCBI
2	Sancho-Martinez I and Martin-Villalba A: Tyrosine phosphorylation and CD95: A FAScinating switch. Cell Cycle. 8:838–842. 2009. View Article : Google Scholar : PubMed/NCBI
3	Eisele G, Roth P, Hasenbach K, Aulwurm S, Wolpert F, Tabatabai G, Wick W and Weller M: APO010, a synthetic hexameric CD95 ligand, induces human glioma cell death in vitro and in vivo. Neuro Oncol. 13:155–164. 2011. View Article : Google Scholar : PubMed/NCBI
4	Konkankit VV, Kim W, Koya RC, Eskin A, Dam MA, Nelson S, Ribas A, Liau LM and Prins RM: Decitabine immunosensitizes human gliomas to NY-ESO-1 specific T lymphocyte targeting through the Fas/Fas ligand pathway. J Transl Med. 9:1922011. View Article : Google Scholar : PubMed/NCBI
5	Zhao JX, Liu XQ and Dong BJ: Primary study of bevacizumab combined with temozolomide for recurrent glioma. Chin Clin Oncol. 39:920–922. 2011.
6	Do N, Weindl G, Grohmann L, Salwiczek M, Koksch B, Korting HC and Schäfer-Korting M: Cationic membrane-active peptides-anticancer and antifungal activity as well as penetration into human skin. Exp Dermatol. 23:326–331. 2014. View Article : Google Scholar : PubMed/NCBI
7	Loud JT, Peters JA, Fraser M and Jenkins J: Applications of advances in molecular biology and genomics to clinical cancer care. Cancer Nurs. 25:110–122. 2002. View Article : Google Scholar : PubMed/NCBI
8	Hopkins AL and Groom CR: The druggable genome. Nat Rev Drug Discov. 1:727–730. 2002. View Article : Google Scholar : PubMed/NCBI
9	Okada M, Sato A, Shibuya K, Watanabe E, Seino S, Suzuki S, Seino M, Narita Y, Shibui S, Kayama T and Kitanaka C: JNK contributes to temozolomide resistance of stem-like glioblastoma cells via regulation of MGMT expression. Int J Oncol. 44:591–599. 2014.PubMed/NCBI
10	Sze CI, Su WP, Chiang MF, Lu CY, Chen YA and Chang NS: Assessing current therapeutic approaches to decode potential resistance mechanisms in glioblastomas. Front Oncol. 3:592013. View Article : Google Scholar : PubMed/NCBI
11	Silber JR, Bobola MS, Blank A and Chamberlain MC: O(6)-methylguanine-DNA methyltransferase in glioma therapy: Promise and problems. Biochim Biophys Acta. 1826:71–82. 2012.PubMed/NCBI
12	Xu JJ, Hong UQ, Zhao W, Hong J, Wen N, Ling QI and Liu XJ: Induction of broccoli polypeptide on apoptosis of C6 glioma cells. Jilin Daxue Xuebao. 39:8–11. 2013.
13	O'Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH and Folkman J: Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 79:315–328. 1994. View Article : Google Scholar : PubMed/NCBI
14	Ferguson SD: Malignant gliomas: Diagnosis and treatment. Dis Mon. 57:558–569. 2011. View Article : Google Scholar : PubMed/NCBI
15	Cobbs CS: Cytomegalovirus and brain tumor: Epidemiology, biology and therapeutic aspects. Curr Opin Oncol. 25:682–688. 2013. View Article : Google Scholar : PubMed/NCBI
16	Dubrez L, Berthelet J and Glorian V: IAP proteins as targets for drug development in oncology. Onco Targets Ther. 9:1285–1304. 2013. View Article : Google Scholar : PubMed/NCBI
17	Bartuzi P, Hofker MH and van de Sluis B: Tuning NF-κB activity: A touch of COMMD proteins. Biochim Biophys Acta. 1832:2315–2321. 2013. View Article : Google Scholar : PubMed/NCBI
18	Fang YQQY, Bai X, Lu XD and Tan Y: Effects of Survivin antisense oligonucleotides on proliferation of hepatic cell line SMMC-7721. Jilin Daxue Xuebao. 39:278–281. 2013.
19	Green DR and Reed JC: Mitochondria and apoptosis. Science. 281:1309–1312. 1998. View Article : Google Scholar : PubMed/NCBI
20	Stuckey DW and Shah K: TRAIL on trial: Preclinical advances in cancer therapy. Trends Mol Med. 19:685–694. 2013. View Article : Google Scholar : PubMed/NCBI
21	Fink MY and Chipuk JE: Survival of HER2-positive breast cancer cells: Receptor signaling to apoptotic control centers. Genes Cancer. 4:187–195. 2013. View Article : Google Scholar : PubMed/NCBI
22	Dabbagh A and Rajaei S: The role of anesthetic drugs in liver apoptosis. Hepat Mon. 13:e131622013. View Article : Google Scholar : PubMed/NCBI
23	Adrain C and Martin SJ: The mitochondrial apoptosome: A killer unleashed by the cytochrome seas. Trends Biochem Sci. 26:390–397. 2001. View Article : Google Scholar : PubMed/NCBI
24	Velde C Vande, Cizeau J, Dubik D, Alimonti J, Brown T, Israels S, Hakem R and Greenberg AH: BNIP3 and genetic control of necrosis-like cell death through the mitochondrial permeability transition pore. Mol Cell Biol. 20:5454–5468. 2000. View Article : Google Scholar : PubMed/NCBI
25	Bo Sun, Jiajing Liu, Jiajun Chen, et al: Experiment studies of novel tumstatin on C6 glioma cells in vitro. Chin J Lab Diag. 20:707–709. 2016.