Cyclin-Dependent Kinase Inhibitors, Roscovitine And Purvalanol, Induce Apoptosis And Autophagy Related To Unfolded Protein Response In Hela Cervical Cancer Cells
| Autor: | Narcin Palavan-Unsal, Pınar Obakan-Yerlikaya, Elif Damla Arisan, Bahar Sarikaya, Ajda Coker-Gurkan, Benan Temizci, Pelin Ozfiliz-Kilbas |
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| Přispěvatelé: | Fen Edebiyat Fakültesi / Faculty of Letters and Sciences Moleküler Biyoloji ve Genetik / Molecular Biology and Genetics |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
FINE-TUNING MOLECULE Time Factors Uterine Cervical Neoplasms Apoptosis POLYAMINE CATABOLIC PATHWAY MEDIATED APOPTOSIS HeLa ACTIVATION 0302 clinical medicine ENDOPLASMIC-RETICULUM STRESS biology Chemistry Kinase General Medicine ER STRESS Endoplasmic Reticulum Stress Cell biology Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Female Programmed cell death Cell Survival CROSSTALK MECHANISMS 03 medical and health sciences Cyclin-dependent kinase Genetics Roscovitine Autophagy Humans Protein Kinase Inhibitors Molecular Biology Cell Proliferation Cell growth Adenine CDK-INHIBITOR Purvalanol IN-VITRO biology.organism_classification 030104 developmental biology Purines Unfolded Protein Response biology.protein Unfolded protein response Cervical cancer Reactive Oxygen Species HeLa Cells |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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