Abstract
Background: Neuroblastoma is one of the most common childhood solid tumors. Because tumor suppressor genes are often hypermethylated in cancers, DNA methylation has emerged as a target for cancer therapeutics. Nanaomycin A, an inhibitor of DNA methyltransferase 3B, which mediates de novo DNA methylation, reportedly induces death in several types of human cancer cells.
Objective: To study the antitumor activity of nanaomycin A against neuroblastoma cell lines and its mechanism.
Methods: The anti-tumor effect of nanaomycin A on neuroblastoma cell lines was evaluated based on cell viability, DNA methylation levels, apoptosis-related protein expression, and neuronal-associated mRNA expression.
Results: Nanaomycin A decreased genomic DNA methylation levels and induced apoptosis in human neuroblastoma cells. Nanaomycin A also upregulated the expression of mRNAs for several genes related to neuronal maturation.
Conclusions: Nanaomycin A is an effective therapeutic candidate for treating neuroblastoma. Our findings also suggest that the inhibition of DNA methylation is a promising anti-tumor therapy strategy for neuroblastoma.
Keywords: Neuroblastoma, DNA methylation, epigenetics, DNA methyltransferase 3B, nanaomycin A, apoptosis.
[http://dx.doi.org/10.1093/jjco/hyx176] [PMID: 29378002]
[http://dx.doi.org/10.1038/nrdp.2016.78] [PMID: 27830764]
[http://dx.doi.org/10.1007/s00441-018-2796-z] [PMID: 29445860]
[PMID: 34796286]
[http://dx.doi.org/10.1038/nrg3230] [PMID: 22641018]
[http://dx.doi.org/10.1038/npp.2012.112] [PMID: 22781841]
[http://dx.doi.org/10.1016/S0092-8674(00)81656-6] [PMID: 10555141]
[http://dx.doi.org/10.1158/0008-5472.CAN-15-3278] [PMID: 27256564]
[http://dx.doi.org/10.18632/oncotarget.25084] [PMID: 29774131]
[http://dx.doi.org/10.1038/nature25480] [PMID: 29489754]
[http://dx.doi.org/10.1038/nature25795] [PMID: 29489755]
[http://dx.doi.org/10.1101/cshperspect.a019505] [PMID: 27194046]
[http://dx.doi.org/10.3389/fphar.2021.701690] [PMID: 34483903]
[http://dx.doi.org/10.1002/pbc.22607] [PMID: 20589651]
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0609] [PMID: 20833755]
[http://dx.doi.org/10.1038/bmt.2012.244] [PMID: 23208313]
[http://dx.doi.org/10.1007/s13277-016-5433-z] [PMID: 27752996]
[http://dx.doi.org/10.1056/NEJM199910143411601] [PMID: 10519894]
[http://dx.doi.org/10.1007/s11523-014-0354-5] [PMID: 25559288]
[http://dx.doi.org/10.3389/fcell.2018.00140] [PMID: 30406101]
[http://dx.doi.org/10.7554/eLife.40757] [PMID: 30468428]
[http://dx.doi.org/10.3390/children5090114] [PMID: 30154341]
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