Flavopiridol's antiproliferative effects in glioblastoma multiforme


Cobanoglu G., DOĞAN TURAÇLI İ., Ozkan A. C., Ekmekci A.

JOURNAL OF CANCER RESEARCH AND THERAPEUTICS, cilt.12, sa.2, ss.811-817, 2016 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 12 Sayı: 2
  • Basım Tarihi: 2016
  • Doi Numarası: 10.4103/0973-1482.172132
  • Dergi Adı: JOURNAL OF CANCER RESEARCH AND THERAPEUTICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.811-817
  • Anahtar Kelimeler: Apoptosis, flavopiridol, glioblastoma multiforme, proliferation, CELL-CYCLE ARREST, DEPENDENT KINASE INHIBITOR, GROWTH-FACTOR RECEPTOR, HUMAN MYELOMA CELLS, TRANSCRIPTIONAL REPRESSION, ADJUVANT TEMOZOLOMIDE, CARCINOMA-CELLS, DOWN-REGULATION, CDK INHIBITORS, CYTOCHROME-C
  • Gazi Üniversitesi Adresli: Evet

Özet

Aim of Study: Glioblastoma multiforme (GBM) is largely refractory to surgical operation, radiotherapy, and chemotherapy in use today. Remaining lifetime accounting for the GBM-affected patients varies between 12 and 16 months generally. The most frequently altered genes in GBM are p53, epidermal growth factor receptor, PTEN, and cyclin-dependent kinase inhibitor 2A. Our aim is to investigate the antiproliferative and apoptotic effects of flavopiridol, a cyclin-dependent kinases and specific phosphokinase inhibitor, on glioblastoma cell lines having different genetic profiles: U87MG, U118MG, and T98G. Materials and Methods: Cell viability and IC50 values were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, protein expressions were determined by Western blot and caspase activities were analyzed by activity kit. Results: Western blot analysis showed down-regulation of the cyclin D1, c-Myc, and p53 protein activities, and up-regulation of p27(KIP1) activity after flavopiridol treatment. Additionally, flavopiridol diminished p-Akt protein levels generally which induces inhibition of proliferation. Conclusion: The present study demonstrated that flavopiridol did not induce caspase-3/7 activation, BIM, and BAX pro-apoptotic proteins but it leads to the expression changes of various proteins that inhibit proliferation and eternity in glioblastoma cell lines which have different genetic alterations.