ISSN: 2577-4360
Authors: Islam MA* Karim T, Sheikh F, Thomas S, Magrabi T and Miller D
Neuroblastoma is derived from the neural crest cells when they are unable to differentiate into mature nerve cells. The clinical hallmark of neuroblastoma is heterogeneous. A subset of neuroblastoma undergoes spontaneous regression while others with unfavorable biology of n-Myc amplification show relentless progression. Current knowledge suggests that Guanine-Rich Oligonucleotides (GRO) are a potential target for anti-cancer drugs. In this study, it has been shown by circular dichroism (CD) that GROs at the promoter regions of the Survivin (SVN-23) gene could form quadruplex in-vitro. Three human neuroblastoma cell lines were used to explore the effect of SVN-23 on different biological properties: cellular growth, differentiation and death. The neuroblastoma cell lines SH-SY5Y and SK-N-AS have a single copy of the MYCN gene (n-Myc amplified), whereas the SK-N-BE2 cell line has multiple copies. In the SK-N-SH cell line, the neuroblastoma cell line consists of both neuronal and epithelial phenotypes, whereas the SH-SY5Y neuroblastoma cell line, which is derived from SK-N-SH cells, are predominantly the epithelioid phenotype. Cellular differentiation of the SVN-23 cell line is induced by the extension of their neurites followed by cell death in the SH-SY5Y cell line, whereas differentiation in the SKN-SH cell line is induced by flattening the cells. Significant growth inhibition has been shown with SVN-23 in n-Myc-amplified SK-N-BE2 cells, (40-75%), whereas modest growth inhibition (10-40%) has been shown in single copy neuroblastoma cell lines (SK-N-AS & SH-SY5Y) by MTT [3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide] assay. This data indicates that SVN-23 is more sensitive to n-Myc amplified neuroblastoma cells than those of neuroblastoma cells with a single copy of n-Myc gene. This sensitivity of SVN-23 is associated with down regulation of survivin protein expression. This data suggest that SVN-23 oligonucleotides could be a potential therapeutic option for unfavorable, n-Myc-amplified groups of human neuroblastoma.
Keywords: Guanine-Rich Oligonucleotides (GRO); Quadruplex; Survivin; Neuroblastoma; MYCN
