ArticleBiochemical pharmacology2009
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.
Article in Biochemical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Effect of Interaction between Chromium(VI) with 17β-Estradiol and Its Metabolites on Breast Cancer Cell Lines MCF-7/WT and MDA-MB-175-VII: Preliminary Study.Molecules (Basel, Switzerland) · 2023Article
- CHUK/IKK-α loss in lung epithelial cells enhances NSCLC growth associated with HIF up-regulation.Life science alliance · 2019Article
- MicroRNA-152 suppresses cisplatin resistance in A549 cells.Oncology letters · 2019Article
- Hypoxia increases chemoresistance in human medulloblastoma DAOY cells via hypoxia‑inducible factor 1α‑mediated downregulation of the CYP2B6, CYP3A4 and CYP3A5 enzymes and inhibition of cell proliferation.Oncology reports · 2019Article
- Research progress on the relationship between lung cancer drug-resistance and microRNAs.Journal of Cancer · 2019Review
- The Effect of Caffeic Acid on Spermatogonial Stem Cell-type A Cryopreservation.Reports of biochemistry & molecular biology · 2018Article
- Roles of NF-κB Signaling in the Regulation of miRNAs Impacting on Inflammation in Cancer.Biomedicines · 2018Review
- 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-one (CHP) inhibits human ovarian cell proliferation by inducing apoptosis.International journal of clinical and experimental pathology · 2015Article
- Porcine epidemic diarrhea virus N protein prolongs S-phase cell cycle, induces endoplasmic reticulum stress, and up-regulates interleukin-8 expression.Veterinary microbiology · 2013Article
- Equol enhances tamoxifen's anti-tumor activity by induction of caspase-mediated apoptosis in MCF-7 breast cancer cells.BMC cancer · 2013Article
- Porcine epidemic diarrhea virus E protein causes endoplasmic reticulum stress and up-regulates interleukin-8 expression.Virology journal · 2013Article
- MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies.ISRN hematology · 2013Article
- Triptolide-induced apoptosis by inactivating nuclear factor-kappa B apoptotic pathway in multiple myeloma in vitro.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2011Article
- Classical swine fever virus NS2 protein promotes interleukin-8 expression and inhibits MG132-induced apoptosis.Virus genes · 2011Article
- Effect of magnetic Fe3O4 nanoparticles with 2-methoxyestradiol on the cell-cycle progression and apoptosis of myelodysplastic syndrome cells.International journal of nanomedicine · 2011Article
- The function of p27 KIP1 during tumor development.Experimental & molecular medicine · 2009Review
- Vanadium-induced apoptosis of HaCaT cells is mediated by c-fos and involves nuclear accumulation of clusterin.The FEBS journal · 2009Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 4 countries.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.