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


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Cecen E., ALTUN Z. S., Ercetin P., AKTAŞ S., Olgun N.

ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, cilt.15, sa.21, ss.9445-9451, 2014 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 15 Sayı: 21
  • Basım Tarihi: 2014
  • Doi Numarası: 10.7314/apjcp.2014.15.21.9445
  • Dergi Adı: ASIAN PACIFIC JOURNAL OF CANCER PREVENTION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.9445-9451
  • Anahtar Kelimeler: Sanguinarine, neuroblastoma, apoptosis, gene expression, BCL-2 FAMILY PROTEINS, DOWN-REGULATION, CANCER-CELLS, ALKALOID SANGUINARINE, MEDIATED APOPTOSIS, CARCINOMA-CELLS, ACTIVATION, CHELERYTHRINE, DEATH, CYCLE
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

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.