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Cyclin-dependent kinase inhibitors, roscovitine and purvalanol, induce apoptosis and autophagy related to unfolded protein response in HeLa cervical cancer cells

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Author
Özfiliz Kılbaş, Pelin
Sarıkaya, Bahar
Obakan Yerlikaya, Pınar
Çoker Gürkan, Ajda
Arısan, Elif Damla
Temizci, Benan
Palavan Ünsal, Zeynep Narçın
Type
Article
Date
2018-10
Language
en_US
Metadata
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Abstract
Roscovitine (Rosc) and purvalanol (Pur) are competitive inhibitors of cyclin-dependent kinases (CDKs) by targeting their ATP-binding pockets. Both drugs are shown to be effective to decrease cell viability and dysregulate the ratio of pro- and anti-apoptotic Bcl-2 family members, which finally led to apoptotic cell death in different cancer cell lines in vitro. It was well established that Bcl-2 family members have distinct roles in the regulation of other cellular processes such as endoplasmic reticulum (ER) stress. The induction of ER stress has been shown to play critical role in cell death/survival decision via autophagy or apoptosis. In this study, our aim was to investigate the molecular targets of CDK inhibitors on ER stress mechanism related to distinct cell death types in time-dependent manner in HeLa cervical cancer cells. Our results showed that Rosc and Pur decreased the cell viability, cell growth and colony formation, induced ER stress-mediated autophagy or apoptosis in time-dependent manner. Thus, we conclude that exposure of cells to CDK inhibitors induces unfolded protein response and ER stress leading to autophagy and apoptosis processes in HeLa cervical cancer cells.
Subject
Roscovitine
Purvalanol
Cervical cancer
ER stress
Autophagy
Apoptosis
ENDOPLASMIC-RETICULUM STRESS
POLYAMINE CATABOLIC PATHWAY
FINE-TUNING MOLECULE
MEDIATED APOPTOSIS
CDK-INHIBITOR
ER STRESS
IN-VITRO
ACTIVATION
CROSSTALK
MECHANISMS
URI
https://doi.org/10.1007/s11033-018-4222-8
https://hdl.handle.net/11413/3441
Collections
  • Makaleler / Articles [140]
  • Pubmed Publications [149]
  • Scopus Publications [724]
  • WoS Publications [1016]

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İstanbul Kültür University

Hakkında |Politika | Kütüphane | İletişim | Send Feedback | Admin

Istanbul Kültür University, Ataköy Campus E5 Karayolu Üzeri Bakırköy 34158, İstanbul / TURKEY
Copyright © İstanbul Kültür University

Creative Commons Lisansı
IKU Institutional Repository, Creative Commons Alıntı-GayriTicari-Türetilemez 4.0 Uluslararası Lisansı ile lisanslanmıştır.

Designed by  UNIREPOS