CDK inhibitors-induced SSAT expression requires NF?B and PPAR? inMCF-7 breast cancer cells

PINAR OBAKAN; ŞEYMA YILDIRIM; MERT BURAK ÖZTÜRK; ÖZGE BERRAK; AJDA ÇOKER GÜRKAN; ELİF DAMLA ARISAN; ZEYNEP NARÇİN ÜNSAL

Makale detayları

CDK inhibitors-induced SSAT expression requires NF?B and PPAR? inMCF-7 breast cancer cells

Yazarlar:

PINAR OBAKAN | ŞEYMA YILDIRIM | MERT BURAK ÖZTÜRK | ÖZGE BERRAK | AJDA ÇOKER GÜRKAN | ELİF DAMLA ARISAN | ZEYNEP NARÇİN ÜNSAL

Yayıncı:

TUBITAK

Dergi:

Turkish Journal of Biology 2015 Vol.39 Issue 5, pp.712-721

Belge Tipi:

Makale

Yayın Tarihi:

12/2015

Belge Dili:

Türkçe

Document ID (Org No.):

2000811848

Sıklık:

İki Aylık

eISSN:

1303-6092

pISSN:

1300-0152

Anahtar kelimeler:

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 N1-acetyltransferase (SSAT) is under the control of transcription factors such as NF?B 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. Although the induction of SSAT by purvalanol resulted in the activation of NF?B at early time points, induction was accomplished by PPARγ 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.

 

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 N1-acetyltransferase (SSAT) is under the control of transcription factors such as NF?B 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. Although the induction of SSAT by purvalanol resulted in the activation of NF?B at early time points, induction was accomplished by PPARγ 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.

Makale detayları

CDK inhibitors-induced SSAT expression requires NF?B and PPAR? inMCF-7 breast cancer cells

Yazarlar:

PINAR OBAKAN | ŞEYMA YILDIRIM | MERT BURAK ÖZTÜRK | ÖZGE BERRAK | AJDA ÇOKER GÜRKAN | ELİF DAMLA ARISAN | ZEYNEP NARÇİN ÜNSAL

Yayıncı:

TUBITAK

Dergi:

Turkish Journal of Biology 2015 Vol.39 Issue 5, pp.712-721

Belge Tipi:

Makale

Yayın Tarihi:

12/2015

Belge Dili:

Türkçe

Document ID (Org No.):

2000811848

Sıklık:

İki Aylık

eISSN:

1303-6092

pISSN:

1300-0152

Polyamines

SSAT

purvalanol

PPAR?

NF?B

Sayı

Makale detayları

CDK inhibitors-induced SSAT expression requires NF?B and PPAR? inMCF-7 breast cancer cells

Yazarlar: PINAR OBAKAN | ŞEYMA YILDIRIM | MERT BURAK ÖZTÜRK | ÖZGE BERRAK | AJDA ÇOKER GÜRKAN | ELİF DAMLA ARISAN | ZEYNEP NARÇİN ÜNSAL

Yayıncı: TUBITAK

Dergi: Turkish Journal of Biology 2015 Vol.39 Issue 5, pp.712-721

Belge Tipi: Makale

Yayın Tarihi: 12/2015

Belge Dili: Türkçe

Document ID (Org No.): 2000811848

Sıklık: İki Aylık

eISSN: 1303-6092

pISSN: 1300-0152

Polyamines

SSAT

purvalanol

PPAR?

NF?B

Sayı

Yazarlar:

PINAR OBAKAN | ŞEYMA YILDIRIM | MERT BURAK ÖZTÜRK | ÖZGE BERRAK | AJDA ÇOKER GÜRKAN | ELİF DAMLA ARISAN | ZEYNEP NARÇİN ÜNSAL

Yayıncı:

TUBITAK

Dergi:

Turkish Journal of Biology 2015 Vol.39 Issue 5, pp.712-721

Belge Tipi:

Makale

Yayın Tarihi:

12/2015

Belge Dili:

Türkçe

Document ID (Org No.):

2000811848

Sıklık:

İki Aylık

eISSN:

1303-6092

pISSN:

1300-0152