Mocetinostat as a Novel Selective Histone Deacetylase Inhibitor in the Promotion of Apoptosis in glioblastoma Cell Line C6 and T98G

被引:0
作者
Khathayer, Firas [1 ]
Mikael, Mohammad Hussein [1 ]
机构
[1] Univ Mosul, Dept Biol, Coll Sci, Mosul, Iraq
来源
BIOMEDICAL AND BIOTECHNOLOGY RESEARCH JOURNAL | 2024年 / 8卷 / 03期
关键词
Apoptosis; differentiation; glioblastoma; invasion; metastasis; mocetinostat; T98G and C6 cell lines; IN-VITRO; MGCD0103; CANCER;
D O I
10.4103/bbrj.bbrj_216_24
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Histone deacetylase (HDAC) enzymes play a crucial role in regulating gene expression and epigenetic alterations in cancer cells. Mocetinostat (MGCD0103) is a novel, isotype-selective HDAC inhibitor that targets Class I (HDAC1, 2, 3, and 8) and Class IV (HDAC11) enzymes. It has been approved for the use in phase II trials for Hodgkin's lymphoma. Methods: In this study, the glioblastoma cell (GBM) lines T98G and C6 were treated with different concentrations of MGCD0103 (0.0, 0.5, 1.0, 1.5, 2.0, and 2.5 mu M). Western blot analysis was used to evaluate protein expression and flow cytometry was employed to assess apoptosis. Results: The results demonstrated that MGCD0103 exerts multiple anti-cancer activities in GBMs. MGCD0103 modulated key signaling pathways, including inhibition of the Phosphatidylinositol 3- kinase (PI3K)/protein kinase B mechanism pathway and suppression of HDAC1 enzyme activity. High doses of MGCD0103 significantly induced apoptosis and suppressed cell proliferation by upregulating the pro-apoptotic protein Bcl-2-associated protein x and downregulating the anti-apoptotic proteins BH3 Interacting Domain Death Agonist and B-cell leukemia/lymphoma 2 protein. In addition, MGCD0103 treatment upregulated the expression of the tumor-suppressor gene and downregulated the E2F1 transcription factor. Furthermore, MGCD0103 facilitated cell differentiation by activating the glial fibrillary acidic protein Glial Fibrillary acidic protein (GFAP) as distinguish marker of astrocytes, and suppressing the undifferentiation markers Inhibitor of Deoxyribonucleic acid binding 2 and N-Myc proto-oncogene protein. Conclusion: This research suggests that MGCD0103 is a promising drug for inhibiting the proliferation, invasion, and migration of GBMs. The findings also provide new insights into the ability of MGCD0103 to induce differentiation in GBMs. Overall, these results indicate that MGCD0103 could be a potent therapeutic agent for the target of glioblastoma.
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页码:328 / 339
页数:12
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