International Journal of Biochemistry & Physiology (IJBP)
ISSN: 2577-4360
Research Article
Guanine Rich Oligonucleotide at Survivin Promoter (SVN23), Kills Effectively in Advance Neuroblastoma with MYCN
Amplification
Abstract
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
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