CDK inhibitors-induced SSAT expression requires NFκB and PPARγ in MCF-7 breast cancer cells
TURKISH JOURNAL OF BIOLOGY, cilt.39, sa.5, ss.712-721, 2015 (SCI-Expanded, Scopus, TRDizin)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 39 Sayı: 5
- Basım Tarihi: 2015
- Doi Numarası: 10.3906/biy-1501-18
- Dergi Adı: TURKISH JOURNAL OF BIOLOGY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, TR DİZİN (ULAKBİM)
- Sayfa Sayıları: ss.712-721
- İstanbul Kültür Üniversitesi Adresli: Evet
Özet
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.