ArticleRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2016
The purine scaffold Hsp90 inhibitor PU-H71 sensitizes cancer cells to heavy ion radiation by inhibiting DNA repair by homologous recombination and non-homologous end joining.
Article in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Does particle radiation have superior radiobiological advantages for prostate cancer cells? A systematic review of in vitro studies.European journal of medical research · 2022Pooled it
- Endoplasmic reticulum stress and the unfolded protein response in lung diseases: molecular pathways and therapeutic interventions.The Journal of pathology · 2026Review
- Utilization of natural products in diverse pathogeneses of diseases associated with single or double DNA strand damage repair.Chinese medicine · 2025Review
- Epichaperome Inhibition by PU-H71-Mediated Targeting of HSP90 Sensitizes Glioblastoma Cells to Alkylator-Induced DNA Damage.Cancers · 2024Article
- A perspective on tumor radiation resistance following high-LET radiation treatment.Journal of cancer research and clinical oncology · 2024Review
- PU-H71 (NSC 750424): a molecular masterpiece that targets HSP90 in cancer and beyond.Frontiers in pharmacology · 2024Review
- Review
- Rational Combinations of PARP Inhibitors with HRD-Inducing Molecularly Targeted Agents.Cancer treatment and research · 2023Review
- Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials.Cancers · 2022Review
- Ganetespib selectively sensitizes cancer cells for proximal and distal spread-out Bragg peak proton irradiation.Radiation oncology (London, England) · 2022Article
- Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing.Cancers · 2021Review
- Exploiting DNA repair pathways for tumor sensitization, mitigation of resistance, and normal tissue protection in radiotherapy.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Particle Therapy for Breast Cancer: Benefits and Challenges.Frontiers in oncology · 2021Review
- Carbon Ion Radiobiology.Cancers · 2020Review
- Low-Dose Hsp90 Inhibitor Selectively Radiosensitizes HNSCC and Pancreatic Xenografts.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- HSP90 inhibitor PU-H71 increases radiosensitivity of breast cancer cells metastasized to visceral organs and alters the levels of inflammatory mediators.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- Heat-shock proteins: chaperoning DNA repair.Oncogene · 2020Review
- Heat shock proteins and DNA repair mechanisms: an updated overview.Cell stress & chaperones · 2018Review
- Strategies to Enhance Radiosensitivity to Heavy Ion Radiation Therapy.International journal of particle therapy · 2018Review
- Drugging the Cancers Addicted to DNA Repair.Journal of the National Cancer Institute · 2017Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposePU-H71 is a purine-scaffold Hsp90 inhibitor developed to overcome limitations of conventional Hsp90 inhibitors. This study was designed to investigate the combined effect of PU-H71 and heavy ion irradiation on human tumor and normal cells. MATERIALS AND
methodsThe effects of PU-H71 were determined by monitoring cell survival by colony formation, and DNA double-strand break (DSB) repair by γ-H2AX foci and immuno-blotting DSB repair proteins. The mode of cell death was evaluated by sub-G1 DNA content (as an indicator for apoptosis), and mitotic catastrophe.
resultsPU-H71 enhanced heavy ion irradiation-induced cell death in three human cancer cell lines, but the drug did not radiosensitize normal human fibroblasts. In irradiated tumor cells, PU-H71 increased the persistence of γ-H2AX foci, and it reduced RAD51 foci and phosphorylated DNA-PKcs, key DSB repair proteins involved in homologous recombination (HR) and non-homologous end joining (NHEJ). In some tumor cell lines, PU-H71 altered the sub-G1 cell fraction and mitotic catastrophe following carbon ion irradiation.
conclusionOur results demonstrate that PU-H71 sensitizes human cancer cells to heavy ion irradiation by inhibiting both HR and NHEJ DSB repair pathways. PU-H71 holds promise as a radiosensitizer for enhancing the efficacy of heavy ion radiotherapy.
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Registered trials
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