title: Promoting effects of sanguinarine on apoptotic gene expression in human neuroblastoma cells.
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.
authors.affiliation: Department of Pediatric Oncology, Adnan Menderes University School of Medicine, Aydin, Turkey E-mail : rececen@adu.edu.tr.
authors.forename: Emre
authors.initials: E
authors.lastname: Cecen
authors.forename: Zekiye
authors.initials: Z
authors.lastname: Altun
authors.forename: Pinar
authors.initials: P
authors.lastname: Ercetin
authors.forename: Safiye
authors.initials: S
authors.lastname: Aktas
authors.forename: Nur
authors.initials: N
authors.lastname: Olgun
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D053119:Benzophenanthridines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D009124:Muscle Proteins / Q000235:genetics; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; D053119:Benzophenanthridines; D007546:Isoquinolines; D009124:Muscle Proteins; C112246:NOL3 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C005705:sanguinarine; D002945:Cisplatin