ArticlePloS one2012
Modulation of the activity of Sp transcription factors by mithramycin analogues as a new strategy for treatment of metastatic prostate cancer.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 59 citations in OpenAlex.
- Preclinical Pharmacokinetic Evaluation of Mithramycin and Mithramycin SA Tryptophan-Conjugated Analog.Pharmaceutics · 2025Article
- Pan-cancer drivers of metastasis.Molecular cancer · 2025Article
- Knockdown of EPS8 expression attenuates the proliferation of enzalutamide-resistant prostate cancer cells.American journal of cancer research · 2024Article
- Controlled Release of DNA Binding Anticancer Drugs from Gold Nanoparticles with Near-Infrared Radiation.Journal of pharmaceutical sciences · 2023Article
- Transcription factor SP1 regulates haptoglobin fucosylation via induction of GDP-fucose transporter 1 in the hepatoma cell line HepG2.Biochemistry and biophysics reports · 2022Article
- Review
- Erb‑B2 Receptor Tyrosine Kinase 2 is negatively regulated by the p53‑responsive microRNA‑3184‑5p in cervical cancer cells.Oncology reports · 2021Observational
- Mithramycin 2'-Oximes with Improved Selectivity, Pharmacokinetics, and Ewing Sarcoma Antitumor Efficacy.Journal of medicinal chemistry · 2020Article
- Article
- Identification of plicamycin, TG02, panobinostat, lestaurtinib, and GDC-0084 as promising compounds for the treatment of central nervous system infections caused by the free-living amebae Naegleria, Acanthamoeba and Balamuthia.International journal for parasitology. Drugs and drug resistance · 2019Article
- Article
- Direct and Indirect Targeting of HOXA9 Transcription Factor in Acute Myeloid Leukemia.Cancers · 2019Review
- The Mithralog EC-7072 Induces Chronic Lymphocytic Leukemia Cell Death by Targeting Tonic B-Cell Receptor Signaling.Frontiers in immunology · 2019Article
- Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- Targeting Transcription Factors for Cancer Treatment.Molecules (Basel, Switzerland) · 2018Review
- Musashi-2, a novel oncoprotein promoting cervical cancer cell growth and invasion, is negatively regulated by p53-induced miR-143 and miR-107 activation.Journal of experimental & clinical cancer research : CR · 2017Article
- Minnelide Inhibits Androgen Dependent, Castration Resistant Prostate Cancer Growth by Decreasing Expression of Androgen Receptor Full Length and Splice Variants.The Prostate · 2017Article
- The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Specific protein 1 depletion attenuates glucose uptake and proliferation of human glioma cells by regulating GLUT3 expression.Oncology letters · 2016Article
- Inhibition of SP1 by the mithramycin analog EC-8042 efficiently targets tumor initiating cells in sarcoma.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deregulated activity of transcription factors (TFs) of the Sp/KLF family, like Sp1, Sp3 and Sp4, and consequent over-expression of Sp-regulated genes occur frequently in human cancers. This provides the rationale for development of inhibitors of Sp TFs as cancer therapeutics. Mithramycin A (MTM-A) is a natural polyketide that binds GC-rich DNA sequences, inhibits activity of Sp TFs and exhibits potent antitumor activity in experimental systems. However, clinical use of MTM-A is limited by the severe toxicity of the compound. Here, we studied two MTM-A analogues, which had been generated by genetically engineering of the MTM-A biosynthetic pathway, and evaluated their activity in human prostate cancer in cell cultures and mouse models. The compounds, named MTM-SDK and MTM-SK, were highly effective in vitro inhibiting proliferation of prostate cancer cells and transcription of Sp-regulated genes by blocking binding of Sp proteins to the gene promoters. When administered to mice, both compounds were well tolerated with maximum tolerated doses of MTM-SDK and MTM-SK, respectively, 4- and 32- fold higher than MTM-A. After systemic administration, both compounds were cleared rapidly from the bloodstream but maintained plasma levels well above the active concentrations required in vitro for inhibition of Sp TF activity and cell proliferation. Consistently, MTM-SDK and MTM-SK inhibited transcription of Sp-regulated genes in prostate tumor xenografts and exhibited potent antitumor activity in subcutaneous and metastatic tumor xenograft models with no or minimal toxicity. Taken together, these data indicate that MTM-SDK and MTM-SK possess significantly improved pharmacological and toxicological properties compared to MTM-A and represent promising drugs for treatment of advanced prostate cancer.
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