ArticleCarcinogenesis2009
alpha-Tocopheryl succinate and derivatives mediate the transcriptional repression of androgen receptor in prostate cancer cells by targeting the PP2A-JNK-Sp1-signaling axis.
Article in Carcinogenesis, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- Hair Thickness Growth Effect of Adenosine Complex in Male-/Female-Patterned Hair Loss via Inhibition of Androgen Receptor Signaling.International journal of molecular sciences · 2024Article
- Protein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2023Review
- Specificity Proteins (Sp) and Cancer.International journal of molecular sciences · 2023Review
- To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling.Cellular and molecular life sciences : CMLS · 2019Review
- Therapeutic targeting of PP2A.The international journal of biochemistry & cell biology · 2018Review
- PP2A as the Main Node of Therapeutic Strategies and Resistance Reversal in Triple-Negative Breast Cancer.Molecules (Basel, Switzerland) · 2017Review
- All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase.The FEBS journal · 2016Review
- miR-222 attenuates cisplatin-induced cell death by targeting the PPP2R2A/Akt/mTOR Axis in bladder cancer cells.Journal of cellular and molecular medicine · 2016Article
- Inhibition of Notch1 signaling overcomes resistance to the death ligand Trail by specificity protein 1-dependent upregulation of death receptor 5.Cell death & disease · 2015Article
- PP2A inhibition as a novel therapeutic target in castration-resistant prostate cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- PP2A inhibitors arrest G2/M transition through JNK/Sp1- dependent down-regulation of CDK1 and autophagy-dependent up-regulation of p21.Oncotarget · 2015Article
- Cardamonin Suppresses TGF-β1-Induced Epithelial Mesenchymal Transition via Restoring Protein Phosphatase 2A Expression.Biomolecules & therapeutics · 2015Article
- Potent inhibitory effect of δ-tocopherol on prostate cancer cells cultured in vitro and grown as xenograft tumors in vivo.Journal of agricultural and food chemistry · 2014Article
- Quantitative iTRAQ LC-MS/MS Proteomics Reveals Transcription Factor Crosstalk and Regulatory Networks in Hypopharyngeal Squamous Cell Carcinoma.Journal of Cancer · 2014Article
- The cannabinoid WIN 55,212-2 decreases specificity protein transcription factors and the oncogenic cap protein eIF4E in colon cancer cells.Molecular cancer therapeutics · 2013Article
- Mechanism of differentiation-enhanced photodynamic therapy for cancer: upregulation of coproporphyrinogen oxidase by C/EBP transcription factors.Molecular cancer therapeutics · 2013Article
- PP2A-Mediated Anticancer Therapy.Gastroenterology research and practice · 2013Review
- Promoter hypomethylation results in increased expression of protein phosphatase 2A in T cells from patients with systemic lupus erythematosus.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Total syntheses of the histone deacetylase inhibitors largazole and 2-epi-largazole: application of N-heterocyclic carbene mediated acylations in complex molecule synthesis.The Journal of organic chemistry · 2011Article
- Histone deacetylase inhibitors stimulate histone H3 lysine 4 methylation in part via transcriptional repression of histone H3 lysine 4 demethylases.Molecular pharmacology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
As part of our effort to understand the mechanism underlying alpha-tocopheryl succinate [vitamin E succinate (VES)]-mediated antitumor effects, we investigated the signaling pathway by which VES suppresses androgen receptor (AR) expression in prostate cancer cells. VES and, to a greater extent, its truncated derivative TS-1 mediated transcriptional repression of AR in prostate cancer cells but not in normal prostate epithelial cells; a finding that underscores the differential susceptibility of normal versus malignant cells to the antiproliferative effect of these agents. This AR repression was attributable to the ability of VES and TS-1 to facilitate the proteasomal degradation of the transcription factor Sp1. This mechanistic link was corroborated by the finding that proteasome inhibitors or ectopic expression of Sp1 protected cells against drug-induced AR ablation. Furthermore, evidence suggests that the destabilization of Sp1 by VES and TS-1 resulted from the inactivation of Jun N-terminal kinases (JNKs) as a consequence of increased phosphatase activity of protein phosphatase 2A (PP2A). Stable transfection of LNCaP cells with the dominant-negative JNK1 plasmid mimicked drug-induced Sp1 repression, whereas constitutive activation of JNK kinase activity or inhibition of PP2A activity by okadaic acid protected Sp1 from VES- and TS-1-induced degradation. From a mechanistic perspective, the ability of VES and TS-1 to activate PP2A activity underscores their broad spectrum of effects on multiple signaling mechanisms, including those mediated by Akt, mitogen-activated protein kinases, nuclear factor kappaB, Sp1 and AR. This pleiotropic effect in conjunction with low toxicity suggests the translational potential for developing TS-1 into potent PP2A-activating agents for cancer therapy.
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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.