ArticleMolecular pharmacology2015
A Peptide mimicking a region in proliferating cell nuclear antigen specific to key protein interactions is cytotoxic to breast cancer.
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Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Recent advances in structural and functional diversities of cancer lncRNA-encoded peptides: current opportunities and challenges for enhancing cancer diagnosis and treatment.Cancer cell international · 2026Review
- The prognostic significance of immunohistochemical expressions of proliferating cell nuclear antigen, P16 and Ki-67 in breast cancer.Frontiers in oncology · 2026Article
- Recent Advances in Therapeutic Peptides: Innovations and Applications in Treating Infections and Diseases.ACS omega · 2025Review
- Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.Frontiers in pharmacology · 2025Review
- Unveiling the therapeutic potential of thymol from Nigella sativa L. seed: selective anticancer action against human breast cancer cells (MCF-7) through down-regulation of Cyclin D1 and proliferative cell nuclear antigen (PCNA) expressions.Molecular biology reports · 2024Article
- The potential of PCNA inhibition as a therapeutic strategy in cervical cancer.Journal of medical virology · 2023Review
- Facts and prospects of peptide in targeted therapy and immune regulation against triple-negative breast cancer.Frontiers in immunology · 2023Review
- NKp44-Derived Peptide Used in Combination Stimulates Antineoplastic Efficacy of Targeted Therapeutic Drugs.International journal of molecular sciences · 2022Article
- TMEM97 is transcriptionally activated by YY1 and promotes colorectal cancer progression via the GSK-3β/β-catenin signaling pathway.Human cell · 2022Article
- Peptide-based delivery of therapeutics in cancer treatment.Materials today. Bio · 2022Review
- Review
- Proliferating cell nuclear antigen directly interacts with androgen receptor and enhances androgen receptor‑mediated signaling.International journal of oncology · 2021Article
- Molecular Targeting of Cancer-Associated PCNA Interactions in Pancreatic Ductal Adenocarcinoma Using a Cell-Penetrating Peptide.Molecular therapy oncolytics · 2020Article
- DNA damage tolerance in stem cells, ageing, mutagenesis, disease and cancer therapy.Nucleic acids research · 2019Review
- Recognition of a Key Anchor Residue by a Conserved Hydrophobic Pocket Ensures Subunit Interface Integrity in DNA Clamps.Journal of molecular biology · 2019Article
- A Novel Probe for Spliceosomal Proteins that Induces Autophagy and Death of Melanoma Cells Reveals New Targets for Melanoma Drug Discovery.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2019Article
- Article
- The Anticancer Activity of a First-in-class Small-molecule Targeting PCNA.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Ubiquitylation at the Fork: Making and Breaking Chains to Complete DNA Replication.International journal of molecular sciences · 2018Review
- Review
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Authors and funding
13 authors at 5 institutions in 1 country.
Shanna J SmithDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.).
Long GuDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.).
Elizabeth A PhippsDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.).
Lacey E DobroleckiDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.).
Karla S MabreyDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.).
Pattie GulleyDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.).
Kelsey L DillehayDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.).
Zhongyun DongDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.).
Gregg B FieldsDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.).
Yun-Ru ChenDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.).
David AnnDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.).
Robert J HickeyDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.).
Linda H MalkasDepartment of Molecular and Cellular Biology (S.J.S., L.G., L.H.M.), Department of Molecular Medicine (R.J.H.), and Department of Diabetes and Metabolic Diseases Research (Y.-R.C., D.A.), Beckman Research Institute at City of Hope, Duarte, California; Department of Medical and Molecular Genetics (E.A.P.) and Department of Medicine (K.S.M., P.G.), Indiana University School of Medicine, Indianapolis, Indiana; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas (L.E.D.); Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (K.L.D., Z.D.); and Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida (G.B.F.) lmalkas@coh.org.
Beckman Research InstituteIndiana University – Purdue University Indianapolis · USCity of Hope · USUniversity of Cincinnati Medical Center · USIndiana University School of Medicine
Funding
Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI XIWEI WU · 1985 to 2026
$86.3MA Structure/function Analysis of a Tumor Specific ProteinR01CA121289 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI MALKAS, LINDA H. · 2007 to 2011
$1.5MNCI NIH HHS P30 CA033572NCI NIH HHS P30-CA033572NCI NIH HHS R01 CA121289NCI NIH HHS R01-CA121289
Abstract
Proliferating cell nuclear antigen (PCNA) is a highly conserved protein necessary for proper component loading during the DNA replication and repair process. Proteins make a connection within the interdomain connector loop of PCNA, and much of the regulation is a result of the inherent competition for this docking site. If this target region of PCNA is modified, the DNA replication and repair process in cancer cells is potentially altered. Exploitation of this cancer-associated region has implications for targeted breast cancer therapy. In the present communication, we characterize a novel peptide (caPeptide) that has been synthesized to mimic the sequence identified as critical to the cancer-associated isoform of PCNA. This peptide is delivered into cells using a nine-arginine linking mechanism, and the resulting peptide (R9-cc-caPeptide) exhibits cytotoxicity in a triple-negative breast cancer cell line, MDA-MB-436, while having less of an effect on the normal counterparts (MCF10A and primary breast epithelial cells). The novel peptide was then evaluated for cytotoxicity using various in vivo techniques, including ATP activity assays, flow cytometry, and clonogenetic assays. This cytotoxicity has been observed in other breast cancer cell lines (MCF7 and HCC1937) and other forms of cancer (pancreatic and lymphoma). R9-cc-caPeptide has also been shown to block the association of PCNA with chromatin. Alanine scanning of the peptide sequence, combined with preliminary in silico modeling, gives insight to the disruptive ability and the molecular mechanism of action of the therapeutic peptide in vivo.
Indexed as
AnimalsBreast NeoplasmsCytotoxinsFemaleHumansMCF-7 CellsMice, Inbred NODMice, KnockoutMice, SCIDMolecular MimicryPeptide FragmentsProliferating Cell Nuclear AntigenProtein BindingProtein Structure, SecondaryProtein Structure, TertiaryRabbitsCytotoxinsPeptide FragmentsProliferating Cell Nuclear Antigen
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