ArticlePloS one2018
Targeting DNA repair with PNKP inhibition sensitizes radioresistant prostate cancer cells to high LET radiation.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 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
- A perspective on tumor radiation resistance following high-LET radiation treatment.Journal of cancer research and clinical oncology · 2024Review
- Base Excision Repair: Mechanisms and Impact in Biology, Disease, and Medicine.International journal of molecular sciences · 2023Review
- Euchromatic histone lysine methyltransferase 2 facilitates radioresistance in prostate cancer by repressing endoplasmic reticulum protein 29 transcription.The Kaohsiung journal of medical sciences · 2023Article
- Preventive role of cinnamaldehyde against tenuazonic acid- and Freund's adjuvant-induced histopathological and biochemical alterations in the mouse model.Frontiers in microbiology · 2023Article
- Basic and translational research on carbon-ion radiobiology.American journal of cancer research · 2023Review
- Zika Virus Induces Mitotic Catastrophe in Human Neural Progenitors by Triggering Unscheduled Mitotic Entry in the Presence of DNA Damage While Functionally Depleting Nuclear PNKP.Journal of virology · 2022Article
- Evaluation of prophylactic efficacy of cinnamaldehyde in murine model against Paradendryphiella arenariae mycotoxin tenuazonic acid-induced oxidative stress and organ toxicity.Scientific reports · 2021Article
- Focused ultrasound radiosensitizes human cancer cells by enhancement of DNA damage.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2021Article
- Nano-Delivery of a Novel Inhibitor of Polynucleotide Kinase/Phosphatase (PNKP) for Targeted Sensitization of Colorectal Cancer to Radiation-Induced DNA Damage.Frontiers in oncology · 2021Article
- Biological Adaptations of Tumor Cells to Radiation Therapy.Frontiers in oncology · 2021Review
- Base excision repair and its implications to cancer therapy.Essays in biochemistry · 2020Review
- The lipogenic LXR-SREBF1 signaling pathway controls cancer cell DNA repair and apoptosis and is a vulnerable point of malignant tumors for cancer therapy.Cell death and differentiation · 2020Article
- SMC1A is associated with radioresistance in prostate cancer and acts by regulating epithelial-mesenchymal transition and cancer stem-like properties.Molecular carcinogenesis · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High linear energy transfer (LET) radiation or heavy ion such as carbon ion radiation is used as a method for advanced radiotherapy in the treatment of cancer. It has many advantages over the conventional photon based radiotherapy using Co-60 gamma or high energy X-rays from a Linear Accelerator. However, charged particle therapy is very costly. One way to reduce the cost as well as irradiation effects on normal cells is to reduce the dose of radiation by enhancing the radiation sensitivity through the use of a radiomodulator. PNKP (polynucleotide kinase/phosphatase) is an enzyme which plays important role in the non-homologous end joining (NHEJ) DNA repair pathway. It is expected that inhibition of PNKP activity may enhance the efficacy of the charged particle irradiation in the radioresistant prostate cancer cell line PC-3. To test this hypothesis, we investigated cellular radiosensitivity by clonogenic cell survival assay in PC-3 cells.12Carbon ion beam of62 MeVenergy (equivalent 5.16 MeV/nucleon) and with an entrance LET of 287 kev/μm was used for the present study. Apoptotic parameters such as nuclear fragmentation and caspase-3 activity were measured by DAPI staining, nuclear ladder assay and colorimetric caspase-3method. Cell cycle arrest was determined by FACS analysis. Cell death was enhanced when carbon ion irradiation is combined with PNKPi (PNKP inhibitor) to treat cells as compared to that seen for PNKPi untreated cells. A low concentration (10μM) of PNKPi effectively radiosensitized the PC-3 cells in terms of reduction of dose in achieving the same survival fraction. PC-3 cells underwent significant apoptosis and cell cycle arrest too was enhanced at G2/M phase when carbon ion irradiation was combined with PNKPi treatment. Our findings suggest that combined treatment of carbon ion irradiation and PNKP inhibition could enhance cellular radiosensitivity in a radioresistant prostate cancer cell line PC-3. The synergistic effect of PNKPi and carbon ion irradiation could be used as a promising method for carbon-ion therapy in radioresistant cells.
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