The DNMT3B Inhibitor Nanaomycin A as a Neuroblastoma Therapeutic Agent

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: DNA methylation; DNA methyltransferase 3B; Neuroblastoma; apoptosis; epigenetics; nanaomycin A.