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

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. | Turkish Journal of Biology Research Article Turk J Biol (2015) 39: 712-721 © TÜBİTAK doi: CDK inhibitors–induced SSAT expression requires NFκB and PPARγ in MCF-7 breast cancer cells Pınar OBAKAN*, Şeyma YILDIRIM**, Mert Burak ÖZTÜRK**, Özge BERRAK, Ajda ÇOKER GÜRKAN, Elif Damla ARISAN, Zeynep Narçin ÜNSAL Department of Molecular Biology and Genetics, Faculty of Science and Letters, İstanbul Kültür University, İstanbul, Turkey Received: Accepted/Published Online: Printed: 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 N1acetyltransferase (SSAT) is under the control of transcription factors such as NFκB and PPARγ. 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.