Valproic acid inhibits the proliferation of SHSY5Y neuroblastoma cancer cells by downregulating URG4/URGCP and CCND1 gene expression

DODURGA Y., Gundogdu G., Tekin V., Koc T., TUFAN N. L., BAĞCI G., ...Daha Fazla

MOLECULAR BIOLOGY REPORTS, cilt.41, sa.7, ss.4595-4599, 2014 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 41 Sayı: 7
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1007/s11033-014-3330-3
  • Dergi Adı: MOLECULAR BIOLOGY REPORTS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.4595-4599
  • Anahtar Kelimeler: Valproic acid, Neuroblastoma, URG4/URGCP, HISTONE DEACETYLASE INHIBITOR, IN-VITRO, APOPTOSIS, GROWTH, ANGIOGENESIS, INSIGHTS, ROLES, VIVO
  • Ankara Üniversitesi Adresli: Evet

Özet

Valproic acid (VPA), used for the treatment of epilepsy and bipolar disorder, regulates several signaling pathways in brain cells. The up-regulated gene 4 (URG4/URGCP) is a novel gene located on 7p13. URG4/URGCP stimulates cyclin D1 (CCND1) mRNA expression, and URG4/URGCP silencing diminishes CCND1 mRNA expression in HepG2 cells. This study was performed to investigate the anti-cancer mechanism of action of VPA by analyzing the expression of novel gene URG4/URGCP, CCND1, p21, p53, p65 (RelA), Bax, and Bcl-2 in SHSY5Y neuroblastoma (NB) cancer cells. Cytotoxic effects of VPA in SHSY5Y were noticed in time and dose dependent manner with the IC50 doses within the range of 0.5-10 mM. IC50 doses in the SHSY5Y were detected as 7.5 mM. Expression profiles were determined by semi quantitative RT-PCR and URG4/URGCP protein change by western blot analysis. Our results suggest that VPA induces cell cycle arrest in SHSY5Y due to the decrease in URG4/URGCP, CCND1 gene expression and the increase in p65. To conclude, VPA may be a prospective agent for the treatment of NB as a single agent or in combination with other drugs. Thus, more studies should be designed to find a safe dose with the best effects of VPA.