CDK inhibitors-induced SSAT expression requires NFκB and PPARγ in MCF-7 breast cancer cells


YERLİKAYA P. O., Yildirim S., Ozturk M. B., RENCÜZOĞULLARI Ö., ÇOKER GÜRKAN A., Arisan E. D., ...More

TURKISH JOURNAL OF BIOLOGY, vol.39, no.5, pp.712-721, 2015 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 39 Issue: 5
  • Publication Date: 2015
  • Doi Number: 10.3906/biy-1501-18
  • Journal Name: TURKISH JOURNAL OF BIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.712-721
  • Istanbul Kültür University Affiliated: Yes

Abstract

The cyclin-dependent kinase (CDK) inhibitors purvalanol and roscovitine are therapeutic agents that control cell proliferation through regulating cell-cycle machinery. They also affect polyamine (PA) metabolism, which is activated in malignant tissues. Therefore, PA catabolism became a remarkable target in cancer therapies. Induction of the PA catabolic enzyme spermidine/spermine N-1-acetyltransferase (SSAT) is under the control of transcription factors such as NF kappa B and PPAR gamma. The purpose of this study was to investigate the therapeutic potential of CDK inhibitors in combination with PAs in MCF-7 breast cancer cells. In order to understand the involvement of PA catabolic enzyme SSAT in this process we also checked its transcriptional regulation in the presence of CDK inhibitors. MCF-7 cells were exposed to CDK inhibitors in the absence or presence of Spd and Spm. Cell viability loss was evaluated by MTT assay. Apoptosis was determined by annexin-V/PI staining using FACS flow. The SSAT transcription level was measured by qRT-PCR. Intracellular PA pool was determined by HPLC. Protein expressions were assessed by western blotting. We found that CDK inhibitors decreased cell viability in a time-dependent manner and induced apoptosis. Co-treatment of Spd or Spm with CDK inhibitors prevented the apoptotic potential of both drugs. Purvalanol increased SSAT expression levels in a time-dependent manner. Although the induction of SSAT by purvalanol resulted in the activation of NF kappa B at early time points, induction was accomplished by PPAR gamma as a late response after purvalanol treatment. We concluded that both transcriptional control mechanisms could be responsible for SSAT regulation in a time-dependent manner.