dc.contributor.author | Batsi, Christina | en |
dc.contributor.author | Markopoulou, Soultana | en |
dc.contributor.author | Kontargiris, Evangelos | en |
dc.contributor.author | Charalambous, Christina | en |
dc.contributor.author | Thomas, Christoforos G. | en |
dc.contributor.author | Christoforidis, Savvas | en |
dc.contributor.author | Kanavaros, Panagiotis E. | en |
dc.contributor.author | Constantinou, Andreas I. | en |
dc.contributor.author | Marcu, Kenneth B. | en |
dc.contributor.author | Kolettas, Evangelos | en |
dc.creator | Batsi, Christina | en |
dc.creator | Markopoulou, Soultana | en |
dc.creator | Kontargiris, Evangelos | en |
dc.creator | Charalambous, Christina | en |
dc.creator | Thomas, Christoforos G. | en |
dc.creator | Christoforidis, Savvas | en |
dc.creator | Kanavaros, Panagiotis E. | en |
dc.creator | Constantinou, Andreas I. | en |
dc.creator | Marcu, Kenneth B. | en |
dc.creator | Kolettas, Evangelos | en |
dc.date.accessioned | 2019-11-04T12:50:15Z | |
dc.date.available | 2019-11-04T12:50:15Z | |
dc.date.issued | 2009 | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/52948 | |
dc.description.abstract | 2-Methoxyestradiol (2-ME2) induces leukemia cells to undergo apoptosis in association with Bcl-2 inactivation but the mechanisms whereby Bcl-2 contributes to protection against programmed cell death in this context remain unclear. Here we showed that 2-ME2 inhibited the proliferation of Jurkat leukemia cells by markedly suppressing the levels of cyclins D3 and E, E2F1 and p21Cip1/Waf1 and up-regulating p16INK4A. Further, 2-ME2 induced apoptosis of Jurkat cells in association with down-regulation and phosphorylation of Bcl-2 (as mediated by JNK), up-regulation of Bak, activation of caspases-9 and -3 and PARP-1 cleavage. To determine the importance and mechanistic role of Bcl-2 in this process, we enforced its expression in Jurkat cells by retroviral transduction. Enforcing Bcl-2 expression in Jurkat cells abolished 2-ME2-induced apoptosis and instead produced a G1/S phase cell cycle arrest in association with markedly increased levels of p27Kip1. Bcl-2 and p27Kip1 were localized mainly in the nucleus in these apoptotic resistant cells. Interestingly, NF-κB activity and p50 levels were increased by 2-ME2 and suppression of NF-κB signaling reduced p27Kip1 expression and sensitized cells to 2-ME2-induced apoptosis. Importantly, knocking-down p27Kip1 in Jurkat Bcl-2 cells sensitized them to spontaneous and 2-ME2-induced apoptosis. Thus, Bcl-2 prevented the 2-ME2-induced apoptotic response by orchestrating a p27Kip1-dependent G1/S phase arrest in conjunction with activating NF-κB. Thus, we achieved a much better understanding of the penetrance and mechanistic complexity of Bcl-2 dependent anti-apoptotic pathways in cancer cells and why Bcl-2 inactivation is so critical for the efficacy of apoptosis and anti-proliferative inducing drugs like 2-ME2. © 2009 Elsevier Inc. | en |
dc.source | Biochemical pharmacology | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-67349208974&doi=10.1016%2fj.bcp.2009.03.017&partnerID=40&md5=0544736a5813aa33b4c3b4b33bc2ad83 | |
dc.subject | NF-κB | el |
dc.subject | article | en |
dc.subject | human | en |
dc.subject | Humans | en |
dc.subject | controlled study | en |
dc.subject | cancer growth | en |
dc.subject | priority journal | en |
dc.subject | protein bcl 2 | en |
dc.subject | protein expression | en |
dc.subject | Cell cycle | en |
dc.subject | Cyclin-Dependent Kinase Inhibitor p27 | en |
dc.subject | immunoglobulin enhancer binding protein | en |
dc.subject | Proto-Oncogene Proteins c-bcl-2 | en |
dc.subject | Apoptosis | en |
dc.subject | human cell | en |
dc.subject | flow cytometry | en |
dc.subject | DNA fragmentation | en |
dc.subject | cyclin dependent kinase inhibitor 1B | en |
dc.subject | cyclin D3 | en |
dc.subject | cyclin E | en |
dc.subject | leukemia cell line | en |
dc.subject | concentration response | en |
dc.subject | Western blotting | en |
dc.subject | 2 methoxyestradiol | en |
dc.subject | 2-Methoxyestradiol (2-ME2) | en |
dc.subject | agar gel electrophoresis | en |
dc.subject | Bcl-2 | en |
dc.subject | caspase 3 | en |
dc.subject | caspase 9 | en |
dc.subject | cell cycle arrest | en |
dc.subject | cell cycle G1 phase | en |
dc.subject | cell cycle S phase | en |
dc.subject | cyclin dependent kinase inhibitor 1 | en |
dc.subject | cyclin dependent kinase inhibitor 2A | en |
dc.subject | Cyclin-Dependent Kinase Inhibitor p21 | en |
dc.subject | Cyclin-Dependent Kinases | en |
dc.subject | Estradiol | en |
dc.subject | G1 Phase | en |
dc.subject | Jurkat Cells | en |
dc.subject | leukemia cell | en |
dc.subject | lipocortin 5 | en |
dc.subject | NF-kappa B | en |
dc.subject | nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1 | en |
dc.subject | p27Kip1 | en |
dc.subject | protein Bak | en |
dc.subject | protein phosphorylation | en |
dc.subject | retrovirus vector | en |
dc.subject | S Phase | en |
dc.subject | transcription factor E2F1 | en |
dc.title | Bcl-2 blocks 2-methoxyestradiol induced leukemia cell apoptosis by a p27Kip1-dependent G1/S cell cycle arrest in conjunction with NF-κB activation | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1016/j.bcp.2009.03.017 | |
dc.description.volume | 78 | |
dc.description.startingpage | 33 | |
dc.description.endingpage | 44 | |
dc.author.faculty | Σχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied Sciences | |
dc.author.department | Τμήμα Βιολογικών Επιστημών / Department of Biological Sciences | |
dc.type.uhtype | Article | en |
dc.description.notes | <p>Manufacturers: Sigma, Germany | en |
dc.description.notes | Cited By :25</p> | en |
dc.source.abbreviation | Biochem.Pharmacol. | en |
dc.contributor.orcid | Constantinou, Andreas I. [0000-0003-0365-1821] | |
dc.gnosis.orcid | 0000-0003-0365-1821 | |