Effect of Retinoic Acid and Cytotoxic Agent Combinations on Cell Cycle Proteins Cyclin D1 and P21 in Neuroblastoma


AKTAŞ S., ALTUN Z. S., Erbayraktar Z., Olgun N.

TURKIYE KLINIKLERI TIP BILIMLERI DERGISI, cilt.30, sa.3, ss.947-951, 2010 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 30 Sayı: 3
  • Basım Tarihi: 2010
  • Doi Numarası: 10.5336/medsci.2008-10373
  • Dergi Adı: TURKIYE KLINIKLERI TIP BILIMLERI DERGISI
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.947-951
  • Anahtar Kelimeler: Neuroblastoma, cyclin-dependent kinase inhibitor p21, CCND1 protein, human, cytotoxins, N-MYC, EXPRESSION, INDUCTION, DIFFERENTIATION, DEFECTS, ARREST, P53
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Objective: Cyclin D1 is a key regulatory protein of cell cycle and this oncogenic activity had been observed in a variety of tumors. P21 is a cyclin dependent kinase inhibitor responsible for cell cycle arrest as a tumor suppressor gene. The studies in the literature about effects of retinoic acid and cytotoxic agents on p21 and cyclin D1 are not satisfactory. The aim of this study is to investigate effects of chemotherapotic agents on expression of cell cycle proteins cylin D1 and P21. Material and Methods: Cisplatin, 0.5 mu mol/L; vincristine, 0.01 mu mol/L; etoposide, 0.1 mu mol/L; cyclophospamide, 2.5 mu mol/L; doxorubicine, 25 nmol/L; and retinoic acid, 0.0001 mol/L; and their combinations were applied to Kelly human neuroblastoma cell line (N-myc positive) for 24 hours. Cyclin D1 and P21 expressions were analysed with immunocytochemistry method. Expressions were recorded as negative, mild, moderate or high. Results: Cyclin D1 and P21 expression changes were observed in application cytotoxic agents alone or combined with retinoic acid in different degrees. However retinoic acid combined with vincristine is the most noticable group to take into consideration by changing the negativity of p21 to high positivity; and degreesing the expression of cyclin D1 compared to non-treated control neuroblastoma cells. Conclusion: Our results indicate that retinoic acid and vincristine combination is most effective in decraasing proliferation. Second effectivity is shared by combination of retinoic acid with etoposide and combination of retinoic acid with cycophospamide. These in vitro results support the idea of indications of these combinations in neuroblastoma accepted as a chronic disease when side effects are taken into consideration.