ArticleOncogene2007
Dose-response transition from cell cycle arrest to apoptosis with selective degradation of Mdm2 and p21WAF1/CIP1 in response to the novel anticancer agent, aminoflavone (NSC 686,288).
Article in Oncogene, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 29 citations in OpenAlex.
- AhR ligand aminoflavone suppresses α6-integrin-Src-Akt signaling to attenuate tamoxifen resistance in breast cancer cells.Journal of cellular physiology · 2018Article
- Downregulation of serum RAB27B confers improved prognosis and is associated with hepatocellular carcinoma progression through PI3K-AKT-P21 signaling.Oncotarget · 2017Article
- Cytidine Deaminase Deficiency Reveals New Therapeutic Opportunities against Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Aminoflavone-loaded EGFR-targeted unimolecular micelle nanoparticles exhibit anti-cancer effects in triple negative breast cancer.Biomaterials · 2016Article
- Article
- Grape seed extract upregulates p21 (Cip1) through redox-mediated activation of ERK1/2 and posttranscriptional regulation leading to cell cycle arrest in colon carcinoma HT29 cells.Molecular carcinogenesis · 2011Article
- Cell death by the quinoxaline dioxide DCQ in human colon cancer cells is enhanced under hypoxia and is independent of p53 and p21.Radiation oncology (London, England) · 2010Article
- MDM4 (MDMX) localizes at the mitochondria and facilitates the p53-mediated intrinsic-apoptotic pathway.The EMBO journal · 2009Article
- p21 in cancer: intricate networks and multiple activities.Nature reviews. Cancer · 2009Review
- H2AX is required for cell cycle arrest via the p53/p21 pathway.Molecular and cellular biology · 2009Article
- Death receptor-induced activation of the Chk2- and histone H2AX-associated DNA damage response pathways.Molecular and cellular biology · 2009Article
- Aminoflavone induces oxidative DNA damage and reactive oxidative species-mediated apoptosis in breast cancer cells.International journal of cancer · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Aminoflavone (AF, NSC 686,288) is beginning clinical trials. It induces replication-mediated histone H2AX phosphorylation, DNA-protein crosslinks and activates p53. Here, we studied p21(CIP1/WAF1) and Mdm2 responses to AF. Although p53 stabilization and phosphorylation at serine 15 increased with dose and time of exposure, Mdm2 and p21(CIP1/WAF1) protein levels displayed a biphasic response, as they accumulated at submicromolar doses and then decreased with increasing AF. As both Mdm2 and p21(CIP1/WAF1) mRNA levels increased with AF concentration without reduction at higher concentrations, we measured the half-lives of Mdm2 and p21(CIP1/WAF1) proteins. Mdm2 and p21(CIP1/WAF1) half-lives were shortened with increasing AF concentrations. Proteasomal degradation appears responsible for the decrease of both Mdm2 and p21(CIP1/WAF1), as MG-132 prevented their degradation and revealed AF-induced Mdm2 polyubiquitylation. AF also induced protein kinase B (Akt) activation, which was reduced with increasing AF concentrations. Suppression of Akt by small interfering RNA was associated with downregulation of Mdm2 and p21(CIP1/WAF1) and with enhanced apoptosis. These results suggest that the cellular responses to AF are determined at least in part by Mdm2 and p21(CIP1/WAF1) protein levels, as well as by Akt activity, leading either to cell cycle arrest when Mdm2 and p21(CIP1/WAF1) are elevated, or to apoptosis when Mdm2 and p21(CIP1/WAF1) are degraded by the proteasome and Akt insufficiently activated to protect against apoptosis.
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What OpenQuestion holds
Registered trials
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.