ArticleGynecologic oncology2010
Inhibition of Sp1-dependent transcription and antitumor activity of the new aureolic acid analogues mithramycin SDK and SK in human ovarian cancer xenografts.
Article in Gynecologic oncology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 57 citations in OpenAlex.
- Replacing Antibiotics with Synergistic Probiotics-Microalgae Consortium in Mud Crab (Antibiotics (Basel, Switzerland) · 2026Article
- Short-Duration HIPEC-Mimetic Mithramycin A Exposure Induces Durable Transcriptional Remodeling Involving Chromatin Regulatory Networks in Colorectal Cancer Models.International journal of molecular sciences · 2026Article
- Exploring the oncogenic roles of T-box transcription factor TBX2 and its potential as a therapeutic target.Biochemical Society transactions · 2025Review
- Targeting the Tumor Epigenetic Regulator SETDB1 for Tumor Therapy.Current cancer drug targets · 2025Review
- SP1/RNASEH2A accelerates the development of hepatocellular carcinoma by regulating EMT.Heliyon · 2023Article
- Mithplatins: Mithramycin SA-Pt(II) Complex Conjugates for the Treatment of Platinum-Resistant Ovarian Cancers.ChemMedChem · 2023Article
- Role of the Ca2+ channel α2δ-1 auxiliary subunit in proliferation and migration of human glioblastoma cells.PloS one · 2022Article
- Inhibition of the c-Myc Oncogene by the Aureolic Acid Group Antibiotics.Doklady. Biochemistry and biophysics · 2021Article
- Review
- Specificity Protein 1: A Protein With a Two-Sided Role in Ischemic Stroke.Frontiers in cellular neuroscience · 2021Review
- The transcription factor Sp1 modulates RNA polymerase III gene transcription by controllingThe Journal of biological chemistry · 2020Article
- Understanding the Role of the Transcription Factor Sp1 in Ovarian Cancer: from Theory to Practice.International journal of molecular sciences · 2020Review
- Sp1-regulated expression of p11 contributes to motor neuron degeneration by membrane insertion of TASK1.Nature communications · 2019Article
- Inhibition of SP1 by the mithramycin analog EC-8042 efficiently targets tumor initiating cells in sarcoma.Oncotarget · 2016Article
- Antitumoral activity of the mithralog EC-8042 in triple negative breast cancer linked to cell cycle arrest in G2.Oncotarget · 2015Article
- Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer.Scientific reports · 2014Article
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- Genome-wide modulation of gene transcription in ovarian carcinoma cells by a new mithramycin analogue.PloS one · 2014Article
- Mithramycin A induces apoptosis by regulating the mTOR/Mcl-1/tBid pathway in androgen-independent prostate cancer cells.Journal of clinical biochemistry and nutrition · 2013Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
objectiveIncreased activity of Sp family of transcription factors is a frequent and critical event in cancer development and progression. Genes governing tumor growth, invasion and angiogenesis are regulated by Sp factors, like Sp1, Sp3 or Sp4, and are frequently over-expressed in tumors. Targeting Sp factors has been explored as a therapeutic approach. Mithramycin (MTM) is a natural antibiotic that binds DNA and inhibit Sp1-dependent transcription. New analogues, named MTM-SDK and MTM-SK, were recently obtained by genetic engineering of the MTM biosynthetic pathway and have demonstrated improved transcriptional and antiproliferative activity in ovarian cancer cell lines in vitro. In the present study we evaluated the activity of the new compounds in human ovarian cancer xenografts.
methodsExpression of Sp1 and target proteins in ovarian cancer specimens and tumor xenografts was assessed by immunohistochemistry. Drug-induced silencing of Sp1-regulated genes in cells and tumor xenograft samples was assessed by quantitative RT-PCR. Toxicity and antitumor activity of the compounds were investigated in healthy and tumor-bearing immunocompromised mice, respectively.
resultsExpression of Sp1 was frequently increased in human epithelial ovarian cancers. MTM-SDK and MTM-SK acted as potent inhibitors of Sp1-dependent transcription both in vitro and in tumor xenografts. Both compounds were well tolerated even after prolonged administration and delayed growth of ovarian tumor xenografts. MTM-SDK was particularly effective against orthotopic tumors leading to a significant increase of survival and delay of tumor progression.
conclusionsMTM-SDK and MTM-SK show relevant activity in vivo and represent interesting candidates for treatment of ovarian cancers.
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