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Biomolecules
Special Issues
PARPs in Cell Death and PARP Inhibitors in Cancers
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PARPs in Cell Death and PARP Inhibitors in Cancers

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (20 July 2024) | Viewed by 9766

Special Issue Editors

Dr. María Isabel Rodríguez

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, 18071 Granada, Spain
Interests: cancer; SWI/SNF complex; PARP
Special Issues, Collections and Topics in MDPI journals
Dr. Josefa León

E-Mail Website
Guest Editor
Biosanitary Research Institute, ibs.Granada, 18012 Granada, Spain
Interests: cancer; cancer-stem-like cells; oxidative stress; circadian clock
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Poly (ADP-ribose) polymerases (PARPs) are a family of related enzymes that participate in many cellular processes such as DNA repair, genomic stability, transcription, replication, mitosis, cell growth, and programmed cell death. Combined with the concept of synthetic lethality, PARP inhibitors are developed to inhibit the growth of cancer cells and kill them. At present, four PARP inhibitors have been approved by the United States Food and Drug Administration for the treatment of ovarian cancer, breast cancer, pancreatic cancer, and other cancers.

Nevertheless, the process in which PARP participates in cells and the mechanism of PARP inhibitors in cancers still need to be constantly explored to develop more application value for PARP and PARP inhibitors.

This Special Issue will include papers about the role of PARPs in cell death and the mechanism and application of PARP inhibitors in cancers. Papers can be research articles or review articles. We look forward to your contribution.

Dr. María Isabel Rodríguez
Prof. Dr. Josefa León
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • PARPs
  • PARP inhibitors
  • cancers
  • cell death
  • DNA repair

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Related Special Issue

Published Papers (4 papers)

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Research

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11 pages, 1233 KiB  
Article
Resveratrol Inhibits Nucleosome Binding and Catalytic Activity of PARP1
by Darya O. Koshkina, Natalya V. Maluchenko, Anna N. Korovina, Angelina A. Lobanova, Alexey V. Feofanov and Vasily M. Studitsky
Biomolecules 2024, 14(11), 1398; https://doi.org/10.3390/biom14111398 - 2 Nov 2024
Viewed by 1225
Abstract
The natural polyphenol resveratrol is a biologically active compound that interacts with DNA and affects the activity of some nuclear enzymes. Its effect on the interaction between nucleosomes and poly(ADP-ribose) polymerase-1 (PARP1) and on the catalytic activity of PARP1 was studied using Western [...] Read more.
The natural polyphenol resveratrol is a biologically active compound that interacts with DNA and affects the activity of some nuclear enzymes. Its effect on the interaction between nucleosomes and poly(ADP-ribose) polymerase-1 (PARP1) and on the catalytic activity of PARP1 was studied using Western blotting, spectrophotometry, electrophoretic mobility shift assay, and single particle Förster resonance energy transfer microscopy. Resveratrol inhibited PARP1 activity at micro- and sub-micromolar concentrations, but the inhibitory effect decreased at higher concentrations due to the aggregation of the polyphenol. The inhibition of PARP1 by resveratrol was accompanied by its binding to the enzyme catalytic center and a subsequent decrease in PARP1 affinity to nucleosomal DNA. Concurrent binding of talazoparib to the substrate binding pocket of PARP1, which occurs in the presence of resveratrol, restores the interaction of PARP1 with nucleosomes, suggesting that the binding sites of resveratrol and talazoparib overlap. The data suggest that resveratrol can be classified as a natural inhibitor of PARP1. Full article
(This article belongs to the Special Issue PARPs in Cell Death and PARP Inhibitors in Cancers)
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14 pages, 3239 KiB  
Article
Radiosensitizing Effect of PARP Inhibition on Chondrosarcoma and Chondrocyte Cells Is Dependent on Radiation LET
by Antoine Gilbert, Mihaela Tudor, Amandine Delaunay, Raphaël Leman, Julien Levilly, Alexandre Atkinson, Laurent Castéra, Anca Dinischiotu, Diana Iulia Savu, Samuel Valable and François Chevalier
Biomolecules 2024, 14(9), 1071; https://doi.org/10.3390/biom14091071 - 27 Aug 2024
Viewed by 1316
Abstract
Chondrosarcoma is a rare malignant tumor that forms in bone and cartilage. The primary treatment involves surgical removal of the tumor with a margin of healthy tissue. Especially if complete surgical removal is not possible, radiation therapy and chemotherapy are used in conjunction [...] Read more.
Chondrosarcoma is a rare malignant tumor that forms in bone and cartilage. The primary treatment involves surgical removal of the tumor with a margin of healthy tissue. Especially if complete surgical removal is not possible, radiation therapy and chemotherapy are used in conjunction with surgery, but with a generally low efficiency. Ongoing researches are focused on understanding the genetic and molecular basis of chondrosarcoma following high linear energy transfer (LET) irradiation, which may lead to treatments that are more effective. The goal of this study is to evaluate the differential effects of DNA damage repair inhibitors and high LET irradiation on chondrosarcoma versus chondrocyte cells and the LET-dependency of the effects. Two chondrosarcoma cell lines with different IDH mutation status and one chondrocyte cell line were exposed to low LET (X-ray) and high LET (carbon ion) irradiation in combination with an Olaparib PARP inhibitor. Cell survival and DNA repair mechanisms were investigated. High LET irradiation drastically reduced cell survival, with a biological efficiency three times that of low LET. Olaparib significantly inhibited PARylation in all the tested cells. A significant reduction in cell survival of both chondrosarcoma and chondrocyte cells was observed following the treatment combining Olaparib and X-ray. PARP inhibition induced an increase in PARP-1 expression and a reduced effect on the cell survival of WT IDH chondrosarcoma cells. No radiosensitizing effect was observed in cells exposed to Olaparib paired with high LET irradiation. NHEJ was activated in response to high LET irradiation, neutralizing the PARP inhibition effect in both chondrosarcoma cell lines. When high LET irradiation is not available, PARP inhibition could be used in combination with low LET irradiation, with significant radiosensitizing effects on chondrosarcoma cells. Chondrocytes may be affected by the treatment combination too, showing the need to preserve normal tissues from radiation fields when this kind of treatment is suggested. Full article
(This article belongs to the Special Issue PARPs in Cell Death and PARP Inhibitors in Cancers)
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Review

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24 pages, 3902 KiB  
Review
Poly(ADP-Ribose) Polymerase (PARP) Inhibitors for Cancer Therapy: Advances, Challenges, and Future Directions
by Denys Bondar and Yevgen Karpichev
Biomolecules 2024, 14(10), 1269; https://doi.org/10.3390/biom14101269 - 9 Oct 2024
Cited by 3 | Viewed by 3536
Abstract
Poly(ADP-ribose) polymerases (PARPs) are crucial nuclear proteins that play important roles in various cellular processes, including DNA repair, gene transcription, and cell death. Among the 17 identified PARP family members, PARP1 is the most abundant enzyme, with approximately 1–2 million molecules per cell, [...] Read more.
Poly(ADP-ribose) polymerases (PARPs) are crucial nuclear proteins that play important roles in various cellular processes, including DNA repair, gene transcription, and cell death. Among the 17 identified PARP family members, PARP1 is the most abundant enzyme, with approximately 1–2 million molecules per cell, acting primarily as a DNA damage sensor. It has become a promising biological target for anticancer drug studies. Enhanced PARP expression is present in several types of tumors, such as melanomas, lung cancers, and breast tumors, correlating with low survival outcomes and resistance to treatment. PARP inhibitors, especially newly developed third-generation inhibitors currently undergoing Phase II clinical trials, have shown efficacy as anticancer agents both as single drugs and as sensitizers for chemo- and radiotherapy. This review explores the properties, characteristics, and challenges of PARP inhibitors, discussing their development from first-generation to third-generation compounds, more sustainable synthesis methods for discovery of new anti-cancer agents, their mechanisms of therapeutic action, and their potential for targeting additional biological targets beyond the catalytic active site of PARP proteins. Perspectives on green chemistry methods in the synthesis of new anticancer agents are also discussed. Full article
(This article belongs to the Special Issue PARPs in Cell Death and PARP Inhibitors in Cancers)
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18 pages, 725 KiB  
Review
Combination Treatment Strategies to Overcome PARP Inhibitor Resistance
by Young-Hwa Soung and Jun Chung
Biomolecules 2023, 13(10), 1480; https://doi.org/10.3390/biom13101480 - 3 Oct 2023
Cited by 5 | Viewed by 2895
Abstract
Poly(ADP-ribose) polymerase (PARP) enzymes have been shown to be essential for DNA repair pathways, including homologous recombination repair (HRR). Cancers with HRR defects (e.g., BRCA1 and BRCA2 mutations) are targets for PARP inhibitors (PARPis) based on the exploitation of “synthetic lethality”. As a [...] Read more.
Poly(ADP-ribose) polymerase (PARP) enzymes have been shown to be essential for DNA repair pathways, including homologous recombination repair (HRR). Cancers with HRR defects (e.g., BRCA1 and BRCA2 mutations) are targets for PARP inhibitors (PARPis) based on the exploitation of “synthetic lethality”. As a result, PARPis offer a promising treatment option for advanced ovarian and breast cancers with deficiencies in HRR. However, acquired resistance to PARPis has been reported for most tumors, and not all patients with BRCA1/2 mutations respond to PARPis. Therefore, the formulation of effective treatment strategies to overcome resistance to PARPis is urgently necessary. This review summarizes the molecular mechanism of therapeutic action and resistance to PARPis, in addition to emerging combination treatment options involving PARPis. Full article
(This article belongs to the Special Issue PARPs in Cell Death and PARP Inhibitors in Cancers)
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