PLX235018

GSE104526: Reversible LSD1 Inhibition with HCI-2509 induces the p53 gene expression signature in high-risk neuroblastoma cells

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Lysine-Specific Demethylase 1 (LSD1) over-expression correlates with poorly differentiated neuroblastoma and predicts poor outcome despite multimodal therapy. We have studied the efficacy of reversible and specific LSD1 inhibition with HCI-2509 in neuroblastoma cell lines and particularly the effect of HCI-2509 on the transcriptomic profile in MYCN amplified NGP cells. Cell survival assays show that HCI-2509 is cytotoxic to poorly differentiated neuroblastoma cell lines in low micromole or lower doses. Transcriptional profiling of NGP cells treated with HCI-2509 shows a significant effect on p53, cell cycle, MYCN and hypoxia pathway gene sets. HCI-2509 results in increased histone methyl marks and p53 levels along with cell cycle arrest in the G2/M phase and inhibition of colony formation of NGP cells. Our findings indicate that LSD1 inhibition with HCI-2509 has a multi-target effect in MYCN amplified high-risk neuroblastoma cells. SOURCE: Sumati Gupta (sumati.gupta@hci.utah.edu) - Gupta Lab Huntsman Cancer Institute