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| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Batsi, C. | en |
| dc.contributor.author | Markopoulou, S. | en |
| dc.contributor.author | Kontargiris, E. | en |
| dc.contributor.author | Charalambous, C. | en |
| dc.contributor.author | Thomas, C. | en |
| dc.contributor.author | Christoforidis, S. | en |
| dc.contributor.author | Kanavaros, P. | en |
| dc.contributor.author | Constantinou, A. I. | en |
| dc.contributor.author | Marcu, K. B. | en |
| dc.contributor.author | Kolettas, E. | en |
| dc.date.accessioned | 2015-11-24T19:33:22Z | - |
| dc.date.available | 2015-11-24T19:33:22Z | - |
| dc.identifier.issn | 1873-2968 | - |
| dc.identifier.uri | https://olympias.lib.uoi.gr/jspui/handle/123456789/23528 | - |
| dc.rights | Default Licence | - |
| dc.subject | Apoptosis/*drug effects | en |
| dc.subject | Cell Cycle/drug effects/genetics | en |
| dc.subject | Cyclin-Dependent Kinase Inhibitor p21/genetics | en |
| dc.subject | Cyclin-Dependent Kinase Inhibitor p27/genetics | en |
| dc.subject | Cyclin-Dependent Kinases/antagonists & inhibitors | en |
| dc.subject | Estradiol/*analogs & derivatives/pharmacology | en |
| dc.subject | G1 Phase/drug effects/*physiology | en |
| dc.subject | Humans | en |
| dc.subject | Jurkat Cells/cytology/*drug effects | en |
| dc.subject | NF-kappa B/*physiology | en |
| dc.subject | Proto-Oncogene Proteins c-bcl-2/*physiology | en |
| dc.subject | S Phase/drug effects/*physiology | en |
| dc.title | Bcl-2 blocks 2-methoxyestradiol induced leukemia cell apoptosis by a p27(Kip1)-dependent G1/S cell cycle arrest in conjunction with NF-kappaB activation | en |
| heal.type | journalArticle | - |
| heal.type.en | Journal article | en |
| heal.type.el | Άρθρο Περιοδικού | el |
| heal.identifier.primary | 10.1016/j.bcp.2009.03.017 | - |
| heal.identifier.secondary | http://www.ncbi.nlm.nih.gov/pubmed/19447221 | - |
| heal.identifier.secondary | http://ac.els-cdn.com/S0006295209001920/1-s2.0-S0006295209001920-main.pdf?_tid=dfc27659d323fd218c69e2c87b80e443&acdnat=1332999304_2a86e691afcf041d1042e826a0711e53 | - |
| heal.language | en | - |
| heal.access | campus | - |
| heal.recordProvider | Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής | el |
| heal.publicationDate | 2009 | - |
| heal.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 p21(Cip1/Waf1) and up-regulating p16(INK4A). 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 p27(Kip1). Bcl-2 and p27(Kip1) were localized mainly in the nucleus in these apoptotic resistant cells. Interestingly, NF-kappaB activity and p50 levels were increased by 2-ME2 and suppression of NF-kappaB signaling reduced p27(Kip1) expression and sensitized cells to 2-ME2-induced apoptosis. Importantly, knocking-down p27(Kip1) 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 p27(Kip1)-dependent G1/S phase arrest in conjunction with activating NF-kappaB. 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. | en |
| heal.journalName | Biochem Pharmacol | en |
| heal.journalType | peer-reviewed | - |
| heal.fullTextAvailability | TRUE | - |
| Appears in Collections: | Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά) - ΙΑΤ | |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Batsi-2009-Bcl-2 blocks 2-metho.pdf | 973.88 kB | Adobe PDF | View/Open Request a copy |
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