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Promoting Effects of Sanguinarine on Apoptotic Gene Expression in Human Neuroblastoma Cells

  • Cecen, Emre (Adnan Menderes University School of Medicine, Department of Pediatric Oncology) ;
  • Altun, Zekiye (Dokuz Eylul University Institute of Oncology, Department of Basic Oncology) ;
  • Ercetin, Pinar (Dokuz Eylul University Institute of Oncology, Department of Basic Oncology) ;
  • Aktas, Safiye (Dokuz Eylul University Institute of Oncology, Department of Basic Oncology) ;
  • Olgun, Nur (Dokuz Eylul University Institute of Oncology, Department of Pediatric Oncology)
  • Published : 2014.11.28

Abstract

Neuroblastoma is the most common extracranial solid tumor in children. Approximately half of the affected patients are diagnosed with high-risk poor prognosis disease, and novel therapies are needed. Sanguinarine is a benzophenanthridine alkaloid which has anti-microbial, anti-oxidant and anti-inflammatory properties. The aim of this study is whether sanguinarine has in vitro apoptotic effects and which apoptotic genes might be affected in the human neuroblastoma cell lines SH-SY5Y (N-myc negative), Kelly (N-myc positive, ALK positive), and SK-N-BE(2). Cell viability was analysed with WST-1 and apoptotic cell death rates were determined using TUNEL. After RNA isolation and cDNA conversion, expression of 84 custom array genes of apoptosis was determined. Sanguinarine caused cell death in a dose dependent manner in all neuroblastoma cell lines except SK-N-BE(2) with rates of 18% in SH-SY5Y and 21% in Kelly human neuroblastoma cells. Cisplatin caused similar apoptotic cell death rates of 16% in SH-SY5Y and 23% in Kelly cells and sanguinarine-cisplatin combinations caused the same rates (18% and 20%). Sanguinarine treatment did not affect apoptototic gene expression but decreased levels of anti-apoptotic genes NOL3 and BCL2L2 in SH-SY5Y cells. Caspase and TNF related gene expression was affected by the sanguinarine-cisplatin combination in SH-SY5Y cells. The expression of regulation of apoptotic genes were increased with sanguinarine treatment in Kelly cells. From these results, we conclude that sanguinarine is a candidate agent against neuroblastoma.

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