The DNMT3B inhibitor nanaomycin A as a neuroblastoma therapeutic agent

Autor: Mineyoshi Aoyama, Kazuya Izumi, Hiromasa Aoki, Hiroki Kakita, Satoru Takeshita, Hiroko Ueda, Yasumichi Inoue, Hidetoshi Hayashi, Yasumasa Yamada
Rok vydání: 2023
Předmět:
Zdroj: Current Cancer Drug Targets. 23
ISSN: 1568-0096
DOI: 10.2174/1568009623666230522113645
Popis: 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.
Databáze: OpenAIRE