Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI32461

Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect

Erica Salvati,1 Carlo Leonetti,1 Angela Rizzo,1 Marco Scarsella,1 Marcella Mottolese,2 Rossella Galati,3 Isabella Sperduti,4 Malcolm F.G. Stevens,5 Maurizio D’Incalci,6 Maria Blasco,7 Giovanna Chiorino,8 Serge Bauwens,9 Béatrice Horard,9 Eric Gilson,9,10 Antonella Stoppacciaro,11 Gabriella Zupi,1 and Annamaria Biroccio1

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Salvati, E. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Leonetti, C. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Rizzo, A. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Scarsella, M. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Mottolese, M. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Galati, R. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Sperduti, I. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Stevens, M. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by D’Incalci, M. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Blasco, M. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Chiorino, G. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Bauwens, S. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Horard, B. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Gilson, E. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Stoppacciaro, A. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Zupi, G. in: PubMed | Google Scholar

1Experimental Chemotherapy Laboratory, 2Pathology Laboratory, 3Laboratory “D,” and 4Biostatistic Laboratory, Regina Elena Cancer Institute, Rome, Italy. 5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom. 6Department of Oncology, “Mario Negri” Institute for Pharmacological Research, Milan, Italy. 7Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain. 8Fondo Edo Tempia, Biella, Italy. 9Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France. 10Service “Biologie des Tumeurs Solides — Génomique — Protéomique,” Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France. 11Experimental Medicine and Pathology, Department II, S. Andrea Hospital, Rome, Italy.

Address correspondence to: Annamaria Biroccio, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, via delle Messi d’Oro 156, 00158 Rome, Italy. Phone: 39-0652662569; Fax: 39-0652662592; E-mail: biroccio@ifo.it.

Find articles by Biroccio, A. in: PubMed | Google Scholar

Published October 11, 2007 - More info

J Clin Invest. https://doi.org/10.1172/JCI32461.
© 2007 The American Society for Clinical Investigation
Published October 11, 2007 - Version history
Received: April 20, 2007; Accepted: June 20, 2007
View PDF
Abstract

Functional telomeres are required for the replicability of cancer cells. The G-rich strand of telomeric DNA can fold into a 4-stranded structure known as the G-quadruplex (G4), whose stabilization alters telomere function limiting cancer cell growth. Therefore, the G4 ligand RHPS4 may possess antitumor activity. Here, we show that RHPS4 triggers a rapid and potent DNA damage response at telomeres in human transformed fibroblasts and melanoma cells, characterized by the formation of several telomeric foci containing phosphorylated DNA damage response factors γ-H2AX, RAD17, and 53BP1. This was dependent on DNA repair enzyme ATR, correlated with delocalization of the protective telomeric DNA–binding protein POT1, and was antagonized by overexpression of POT1 or TRF2. In mice, RHPS4 exerted its antitumor effect on xenografts of human tumor cells of different histotype by telomere injury and tumor cell apoptosis. Tumor inhibition was accompanied by a strong DNA damage response, and tumors overexpressing POT1 or TRF2 were resistant to RHPS4 treatment. These data provide evidence that RHPS4 is a telomere damage inducer and that telomere disruption selectively triggered in malignant cells results in a high therapeutic index in mice. They also define a functional link between telomere damage and antitumor activity and reveal the key role of telomere-protective factors TRF2 and POT1 in response to this anti-telomere strategy.

Version history
  • Version 1 (October 11, 2007): No description
  • Version 2 (November 1, 2007): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts