The antagonistic effects of temozolomide and trichostatin a combination on MGMT and DNA mismatch repair pathways in Glioblastoma.
Humans
Temozolomide
/ pharmacology
Glioblastoma
/ drug therapy
Dacarbazine
/ pharmacology
Antineoplastic Agents, Alkylating
/ pharmacology
DNA Mismatch Repair
Cell Line, Tumor
Brain Neoplasms
/ drug therapy
DNA Repair Enzymes
/ genetics
DNA Modification Methylases
/ genetics
Drug Resistance, Neoplasm
Tumor Suppressor Proteins
/ genetics
DNA repair
Glioblastoma
Temozolomide
Trichostatin A
Journal
Medical oncology (Northwood, London, England)
ISSN: 1559-131X
Titre abrégé: Med Oncol
Pays: United States
ID NLM: 9435512
Informations de publication
Date de publication:
05 Jul 2023
05 Jul 2023
Historique:
received:
28
04
2023
accepted:
02
06
2023
medline:
6
7
2023
pubmed:
5
7
2023
entrez:
4
7
2023
Statut:
epublish
Résumé
Glioblastoma is the most aggressive and fatal form of brain cancer. Despite new advancements in treatment, the desired outcomes have not been achieved. Temozolomide (TMZ) is the first-choice treatment for the last two decades and has improved survival rates. Emerging studies have shown that targeting epigenetics in glioblastoma can be beneficial when combined with clinically used treatments. Trichostatin A (TSA), a histone deacetylase inhibitor, has anti-cancer properties in various cancers. No data concerning the TMZ and TSA relationship was shown previously in glioblastoma therefore, we aimed to determine the likely therapeutic effect of the TMZ and TSA combination in glioblastoma. The T98G and U-373 MG, glioblastoma cell lines, were used in this study. TMZ and TSA cytotoxicity and combination index were performed by MTT assay. The expression of DNA repair genes (MGMT, MLH-1, PMS2, MSH2 and MSH6) was detected using RT-PCR. One-way analysis of variance (ANOVA) was used for statistical analysis. Combination index calculations revealed antagonistic effects of TMZ and TSA in terms of cytotoxicity. Antagonistic effects were more apparent in the T98G cell line, which is expressing MGMT relatively higher. MGMT and DNA Mismatch Repair (MMR) genes were upregulated in the T98G cell line, whereas downregulated in the U373-MG cell lines under TMZ and TSA combination treatment. It is concluded that MGMT might be playing a more active part than MMR genes in TMZ resistance to TMZ and TSA antagonism. This is the first study elucidating the TMZ and TSA relationship in cancer cell lines.
Identifiants
pubmed: 37403006
doi: 10.1007/s12032-023-02079-6
pii: 10.1007/s12032-023-02079-6
doi:
Substances chimiques
Temozolomide
YF1K15M17Y
trichostatin A
3X2S926L3Z
Dacarbazine
7GR28W0FJI
Antineoplastic Agents, Alkylating
0
DNA Repair Enzymes
EC 6.5.1.-
DNA Modification Methylases
EC 2.1.1.-
MGMT protein, human
EC 2.1.1.63
Tumor Suppressor Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
223Subventions
Organisme : Yüzüncü Yil Üniversitesi
ID : Yüzüncü Yil Üniversitesi
Organisme : Türkiye Bilimsel ve Teknolojik Araştırma Kurumu
ID : 1919B011802106
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Ostrom QT, et al. CBTRUS Statistical Report: primary brain and other Central Nervous System Tumors diagnosed in the United States in 2015–2019. Neuro Oncol. 2022;24(5):v1–v. https://doi.org/10.1093/neuonc/noac202 .
doi: 10.1093/neuonc/noac202
pubmed: 36196752
Tykocki T, Eltayeb M. Ten-year survival in glioblastoma. A systematic review. J Clin Neurosci. 2018;54:7–13. https://doi.org/10.1016/j.jocn.2018.05.002 .
doi: 10.1016/j.jocn.2018.05.002
pubmed: 29801989
Louis DN, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021;23(8):1231–51. https://doi.org/10.1093/neuonc/noab106 .
doi: 10.1093/neuonc/noab106
pubmed: 34185076
pmcid: 8328013
Silvani A. New perspectives: glioma in adult patients. Tumori J. p. Mar. 2023;030089162311597. https://doi.org/10.1177/03008916231159716 .
Ståhl P, Henoch I, Smits A, Rydenhag B, Ozanne A. Quality of life in patients with glioblastoma and their relatives. Acta Neurol Scand. 2022;146(1):82–91. https://doi.org/10.1111/ane.13625 .
doi: 10.1111/ane.13625
pubmed: 35470866
pmcid: 9324166
Shi J, Dong B, Zhou P, Guan W, Peng Y. Functional network analysis of gene-phenotype connectivity associated with temozolomide. Oncotarget. 2017;8(50):87554–67. https://doi.org/10.18632/oncotarget.20848 .
doi: 10.18632/oncotarget.20848
pubmed: 29152101
pmcid: 5675653
Liu EK, Sulman EP, Wen PY, Kurz SC. Novel therapies for Glioblastoma. Curr Neurol Neurosci Rep. 2020;20(7). https://doi.org/10.1007/s11910-020-01042-6 .
Lee P, et al. Mechanisms and clinical significance of histone deacetylase inhibitors: epigenetic glioblastoma therapy. Anticancer Res. 2015;35(2):615–25.
pubmed: 25667438
pmcid: 6052863
Kunadis E, Lakiotaki E, Korkolopoulou P, Piperi C. Targeting post-translational histone modifying enzymes in glioblastoma. Pharmacol Ther. 2021;220:107721. https://doi.org/10.1016/j.pharmthera.2020.107721 .
doi: 10.1016/j.pharmthera.2020.107721
pubmed: 33144118
Zhang Y, Carr T, Dimtchev A, Zaer N, Dritschilo A, Jung M. Attenuated DNA damage repair by trichostatin a through BRCA1 suppression. Radiat Res. 2007;168(1):115–24. https://doi.org/10.1667/RR0811.1 .
doi: 10.1667/RR0811.1
pubmed: 17722998
Perla A, et al. Histone deacetylase inhibitors in Pediatric Brain Cancers: Biological Activities and therapeutic potential. Front Cell Dev Biol. 2020;8:1–14. https://doi.org/10.3389/fcell.2020.00546 .
doi: 10.3389/fcell.2020.00546
Taspinar Çakir, Güven, Denizler K, Rüstemoğlu. “The Effect of Trichostatin A on Radiosensitivity in Glioblastoma,” Proceedings, vol. 40, no. 1, p. 22, 2019, https://doi.org/10.3390/proceedings2019040022 .
Savran B, Yerlikaya A, Erdoğan E, Genç O. “Anticancer Agent Ukrain and Bortezomib Combination is Synergistic in 4T1 Breast Cancer Cells,” Anticancer. Agents Med. Chem, vol. 14, no. 3, pp. 466–472, Feb. 2014, https://doi.org/10.2174/18715206113139990318 .
Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621–81. https://doi.org/10.1124/pr.58.3.10 .
doi: 10.1124/pr.58.3.10
pubmed: 16968952
Lan F, Yang Y, Han J, Wu Q, Yu H, Yue X. Sulforaphane reverses chemo-resistance to temozolomide in glioblastoma cells by NF-κB-dependent pathway downregulating MGMT expression. Int J Oncol. 2016;48(2):559–68. https://doi.org/10.3892/ijo.2015.3271 .
doi: 10.3892/ijo.2015.3271
pubmed: 26648123
Staberg M, Michaelsen SR, Rasmussen RD, Villingshøj M, Poulsen HS, Hamerlik P. Inhibition of histone deacetylases sensitizes glioblastoma cells to lomustine. Cell Oncol. 2017;40(1):21–32. https://doi.org/10.1007/s13402-016-0301-9 .
doi: 10.1007/s13402-016-0301-9
Kato Y, et al. Contributing factors of temozolomide resistance in MCF-7 tumor xenograft models. Cancer Biol Ther. 2007;6(6):891–7. https://doi.org/10.4161/cbt.6.6.4096 .
doi: 10.4161/cbt.6.6.4096
pubmed: 17582214
Kitange GJ, et al. Induction of MGMT expression is associated with temozolomide resistance in glioblastoma xenografts. Neuro Oncol. 2009;11(3):281–91. https://doi.org/10.1215/15228517-2008-090 .
doi: 10.1215/15228517-2008-090
pubmed: 18952979
pmcid: 2718972
Perazzoli G, et al. Temozolomide resistance in glioblastoma cell lines: implication of MGMT, MMR, P-glycoprotein and CD133 expression. PLoS ONE. 2015;10(10):1–23. https://doi.org/10.1371/journal.pone.0140131 .
doi: 10.1371/journal.pone.0140131
Meng CF, Zhu XJ, Peng G, Dai DQ. Role of histone modifications and DNA methylation in the regulation of O6-methylguanine-DNA methyltransferase gene expression in human stomach cancer cells. Cancer Invest. 2010;28(4):331–9. https://doi.org/10.3109/07357900903179633 .
doi: 10.3109/07357900903179633
pubmed: 19857042
Danam RP, Howell SR, Brent TP, Harris LC. Epigenetic regulation of O6-methylguanine-DNA methyltransferase gene expression by histone acetylation and methyl-CpG binding proteins. Mol Cancer Ther. 2005;4(1):61–9. https://doi.org/10.1158/1535-7163.61.4.1 .
doi: 10.1158/1535-7163.61.4.1
pubmed: 15657354
Bhakat KK, Mitra S. Regulation of the human O6-methylguanine-DNA methyltransferase gene by transcriptional coactivators cAMP response element-binding protein-binding protein and p300. J Biol Chem. 2000;275(44):34197–204. https://doi.org/10.1074/jbc.M005447200 .
doi: 10.1074/jbc.M005447200
pubmed: 10942771
Shinsato Y, et al. Reduction of MLH1 and PMS2 confers temozolomide resistance and is associated with recurrence of glioblastoma. Oncotarget. 2013;4(12):2261–70. https://doi.org/10.18632/oncotarget.1302 .
doi: 10.18632/oncotarget.1302
pubmed: 24259277
pmcid: 3926825
Meng CF, Su B, Li W. DNA demethylation is superior to histone acetylation for reactivating cancer-associated genes in ovarian cancer cells. Mol Med Rep. 2011;4(6):1273–8. https://doi.org/10.3892/mmr.2011.557 .
doi: 10.3892/mmr.2011.557
pubmed: 21850374
Imesch P, Dedes KJ, Furlato M, Fink D, Fedier A. MLH1 protects from resistance acquisition by the histone deacetylase inhibitor trichostatin A in colon tumor cells. Int J Oncol. 2009;35(3):631–40. https://doi.org/10.3892/ijo_00000375 .
doi: 10.3892/ijo_00000375
pubmed: 19639184
Kondo Y, Shen L, Issa J-PJ. Critical role of histone methylation in tumor suppressor gene silencing in Colorectal Cancer. Mol Cell Biol. 2003;23(1):206–15. https://doi.org/10.1128/mcb.23.1.206-215.2003 .
doi: 10.1128/mcb.23.1.206-215.2003
pubmed: 12482974
pmcid: 140684
McFaline-Figueroa JL, et al. Minor changes in expression of the mismatch repair protein MSH2 exert a major impact on glioblastoma response to temozolomide. Cancer Res. 2015;75:3127–38. https://doi.org/10.1158/0008-5472.CAN-14-3616 .
doi: 10.1158/0008-5472.CAN-14-3616
pubmed: 26025730
pmcid: 4526337
Castro GN, et al. Effects of temozolomide (TMZ) on the expression and interaction of heat shock proteins (HSPs) and DNA repair proteins in human malignant glioma cells. Cell Stress Chaperones. 2015;20(2):253–65. https://doi.org/10.1007/s12192-014-0537-0 .
doi: 10.1007/s12192-014-0537-0
pubmed: 25155585
Ponnusamy L, Mahalingaiah PKS, Chang YW, Singh KP. “Reversal of epigenetic aberrations associated with the acquisition of doxorubicin resistance restores drug sensitivity in breast cancer cells,” Eur. J. Pharm. Sci, vol. 123, no. June, pp. 56–69, 2018, https://doi.org/10.1016/j.ejps.2018.07.028 .