Yayın: CDK inhibitors-induced SSAT expression requires NF kappa B and PPAR gamma in MCF-7 breast cancer cells
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Tarih
2015
Yazarlar
Obakan Yerlikaya, Pınar
Yıldırım, Şeyma
Öztürk, Mert Burak
Berrak, Özge
Çoker Gürkan, Ajda
Arısan, Elif Damla
Ünsal Palavan, Zeynep Narçın
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayımcı
TUBİTAK Scientific & Technical Research Council Turkey, Ataturk Bulvarı No 221, Kavaklıdere, Ankara, 00000, Turkey
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.
Açıklama
Anahtar kelimeler
Polyamines, SSAT, Purvalanol, PPAR gamma, NF kappa B, Spermidine/Spermine N-1-Acetyltransferase SSAT, Induced Apoptosis, Colon-Cancer, Polyamine Metabolism, Carcinoma Cells, Activation, Induction, Roscovitine, Autophagy, Alpha