Neuroblastoma is a childhood
tumor with a poor survival in advanced stage disease despite intensive chemotherapeutic regimes. The new
histone deacetylase (
HDAC) inhibitor BL1521 has shown promising results in
neuroblastoma. Inhibition of HDAC resulted in a decrease in proliferation and metabolic activity, induction of apoptosis and differentiation of
neuroblastoma cells. In order to elucidate the mechanism mediating the effects of
BL1521 on
neuroblastoma cells, we investigated the gene expression profile of an MYCN single copy (SKNAS) and an MYCN amplified (IMR32)
neuroblastoma cell line
after treatment with
BL1521 using the Affymetrix
oligonucleotide array U133A. An altered expression of 255 genes was observed in both
neuroblastoma cell lines. The majority of these genes were involved in gene expression, cellular metabolism, and cell signaling. We observed changes in the expression of vital genes belonging to the cell cycle (
cyclin D1 and CDK4) and apoptosis (BNIP3, BID, and BCL2) pathway in response to
BL1521. The expression of 37 genes was altered by both
BL1521 and
Trichostatin A, which could indicate a common gene set regulated by different
HDAC inhibitors.
BL1521 treatment changed the expression of a number of MYCN-associated genes. Several genes in the Wnt and the Delta/Notch pathways were changed in response to
BL1521 treatment, suggesting that
BL1521 is able to induce the differentiation of
neuroblastoma cells into a more mature phenotype.