Background:
Neuroblastoma (NB) is the most common extracranial solid tumor in children. Despite advances in therapy, the prognosis of high-risk NB remains poor. Thus, alternate options of therapy are required to improve the survival rate and reduce the side-effects of existing therapies in neuroblastoma patients. Histone deacetylase (HDAC) proteins modulate transcription by deacetylation of the lysine residues in the histone tails of the chromatin and of several non-histone proteins. HDAC inhibitors comprise a diverse class of compounds targeting these HDAC proteins and are being rigorously studied for their role in several types of cancers. The aim of the present study was to investigate the antitumor effects of a novel HDAC inhibitor, OBP-801, as a potential therapeutic agent for treating NB.
Methods:
Human NB cell lines IMR32, GOTO, SK-N-AS, and SH-SY5Y were used in this study. Cell survival rate was evaluated by the WST-8 assay; cell cycle was analyzed by flow cytometry. Apoptosis was detected by Annexin V staining and analyzed by flow cytometry.
Results:
Induction of apoptosis and cell cycle arrest at the G2/M phase was observed in all the NB cell lines studied after 24-h exposure to pharmacological levels of OBP-801. Concentrations of OBP-801 required for 50% inhibition of proliferation for IMR32, GOTO, SK-N-AS, and SH-SY5Y were 1.5 ± 0.9 nM, 2.5 ± 1.1 nM, 3.6 ± 1.4 nM, and 2.6 ± 1.1 nM, respectively.
Conclusion:
Our results suggest that the novel HDAC inhibitor OBP-801 is a broad-range and effective inhibitor of NB cell lines and can be a potent therapeutic option for NB.