Investigation of the effects of a sulfite molecule on human neuroblastoma cells via a novel oncogene URG4/URGCP.

Abstract Aim The aim of this study is to determine the anticancer effect of sulfite on SH-SY5Y neuroblastoma cells in vitro conditions and elucidate underlying molecular mechanism of sulfite and explore its therapeutic activity. Main methods In this study, cytotoxic effects of sulfite in SH-SY5Y cells were detected over time in a dose dependent manner with the IC 50 doses ranging from 0.5 to10 mM. Genotoxic effect of sulfite was shown by comet assay. IC 50 doses in the SH-SY5Y cells were detected as 5 mM. Expression profiles of the target genes related to apoptosis and cell cycle control were determined by quantitative RT-PCR. Protein changes were determined by western blot analysis. Key findings URG4 / URGCP , CCND1 , CCND2 , CDK4 , CDK6 , E2F4 and BCL-2 gene expression levels were significantly reduced and RB1 , TP53 , BAX , BID , CASP2 , CASP3 , CASP9 and DIABLO gene expressions were significantly increased in dose group cells. The mechanism of this result may be related to sulfite dependent inhibition of cell cycle at the G1 phase by down-regulating URG4 / URGCP or CCND1 , CDK4 , CDK6 gene expression and stimulating apoptosis via the intrinsic pathway. Sulfite suppressed invasion and colony formation in SH-SY5Y cell line using matrigel invasion chamber and colony formation assay, respectively. Significance It is thought that sulfite demonstrates anticarcinogenesis activity by affecting cell cycle arrest, apoptosis, invasion, and colony formation on SH-SY5Y cells. Sulfite may be an effective agent for treatment of neuroblastoma as a single agent or in combination with other agents.