Role of condensates in modulating DNA repair pathways and its implication for chemoresistance

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(6), P. 104800 - 104800

Published: May 9, 2023

For cells, it is important to repair DNA damage, such as double-strand and single-strand breaks, because unrepaired can compromise genetic integrity, potentially leading cell death or cancer. Cells have multiple damage pathways that been the subject of detailed genetic, biochemical, structural studies. Recently, scientific community has started gain evidence breaks may occur within biomolecular condensates also contribute through concentrating genotoxic agents used treat various cancers. Here, we summarize key features note where they implicated in breaks. We describe suggesting be involved other types including nucleotide modifications (e.g., mismatch oxidized bases), bulky lesions, among others. Finally, discuss old new mysteries could now addressed considering properties condensates, chemoresistance mechanisms. Chemical changes highly harmful living organisms. DNA, like molecules, undergo chemical reactions. 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Language: Английский

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Chemical Insights into Oxidative and Nitrative Modifications of DNA

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15240 - 15240

Published: Oct. 16, 2023

This review focuses on DNA damage caused by a variety of oxidizing, alkylating, and nitrating species, it may play an important role in the pathophysiology inflammation, cancer, degenerative diseases. Infection chronic inflammation have been recognized as factors carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS) nitrogen (RNS) are generated from epithelial cells, result formation oxidative nitrative lesions, such 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) 8-nitroguanine. Cellular is continuously exposed to very high level genotoxic stress physical, chemical, biological agents, with estimated 10,000 modifications occurring every hour genetic material each our cells. highlights recent developments chemical biology toxicology 2'-deoxyribose oxidation products DNA.

Language: Английский

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Beyond cisplatin: New frontiers in metallodrugs for hard-to-treat triple negative breast cancer

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 499, P. 215507 - 215507

Published: Oct. 27, 2023

Language: Английский

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Strategy of targeting the tumor microenvironment via inhibition of fibroblast/fibrosis remodeling new era to cancer chemo-immunotherapy resistance

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 957, P. 175991 - 175991

Published: Aug. 23, 2023

Language: Английский

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The role of lncRNA NEAT1 in human cancer chemoresistance

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 5, 2024

Abstract Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance an important reason for poor efficacy and prognosis, which has become urgent problem to be solved field chemotherapy. Therefore, it very deeply study analyze mechanism its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) been shown closely associated with cancer. NEAT1 induces cell chemotherapeutic drugs by regulating apoptosis, cycle, drug transport metabolism, DNA damage repair, EMT, autophagy, stem characteristics, metabolic reprogramming. This indicates that may target overcome expected a potential biomarker predict effect article summarizes expression characteristics different cancers, discusses role related molecular mechanisms, aiming clarify as new feasibility sensitizers, view providing therapeutic direction overcoming dilemma future.

Language: Английский

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Oral Cancer Stem Cells: A Comprehensive Review of Key Drivers of Treatment Resistance and Tumor Recurrence

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177222 - 177222

Published: Jan. 1, 2025

Language: Английский

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Global, regional, and national burden of malignant neoplasm of bone and articular cartilage in adults aged 65 years and older, 1990–2021: a systematic analysis based on the global burden of disease study 2021

Aging Clinical and Experimental Research, Journal Year: 2025, Volume and Issue: 37(1)

Published: Jan. 8, 2025

Abstract Background This study aims to delineate the global, regional, and national burden of malignant neoplasms bone articular cartilage (MNBAC) among individuals aged 65 years older from 1990 2021, stratified by age, sex, sociodemographic index (SDI). Methods We harnessed data Global Burden Disease Study 2021 evaluate prevalence, incidence, mortality, disability-adjusted life (DALYs) associated with MNBAC across 204 countries territories between 2021. The socio-demographic Index (SDI) served as a metric examine influence socioeconomic development on MNBAC. Furthermore, joinpoint regression analysis was employed identify marked most significant temporal changes over period. Results In an estimated 163,561 prevalent cases were recorded ≥ years, alongside 28,100 newly diagnosed cases, 27,588 deaths, 508,202 DALYs. age-standardized rates per 100,000 population 21.30 for 3.69 3.66 65.85 Notably, Cuba reported highest prevalence rate (42.42), while Philippines exhibited greatest DALY (161.78). Egypt demonstrated incidence (7.44) mortality (8.90). A inverse correlation observed SDI regions. Conclusions underscores substantial global adults, accentuating imperative tailored public health interventions, advancements in diagnostic therapeutic approaches, particularly within resource-constrained settings.

Language: Английский

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Calcium hydroxide nanoparticles induce cell death, genomic instability, oxidative stress and apoptotic gene dysregulation on human HepG2 cells

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 23, 2025

Abstract Calcium hydroxide nanoparticles (Ca(OH) 2 NPs) possess potent antimicrobial activities and unique physical chemical properties, making them valuable across various fields. However, limited information exists regarding their effects on genomic DNA integrity potential to induce apoptosis in normal cancerous human cell lines. This study thus aimed evaluate the impact of Ca(OH) NPs viability, integrity, oxidative stress induction skin fibroblasts (HSF) hepatic (HepG2) cells. Cell viability stability were assessed using Sulforhodamine B (SRB) assay alkaline comet assay, respectively. Reactive oxygen species (ROS) levels measured 2,7-dichlorofluorescein diacetate, while expression level apoptosis-related genes (p53, Bax, Bcl-2) quantified real-time PCR (qRT-PCR). The SRB cytotoxicity revealed that a 48-hour exposure caused concentration-dependent death proliferation inhibition both HSF HepG2 cells, with IC50 values 271.93 µg/mL for 291.8 Treatment concentration selectively induced significant damage, excessive ROS generation, marked dysregulation apoptotic (p53 Bax) anti-apoptotic (Bcl-2) gene triggering apoptosis. In contrast, cells no changes or expression. These findings indicate exhibit was non-genotoxic inducing genotoxicity cancer through breaks ROS-mediated mechanisms. Further studies are required explore biological toxicological properties therapeutic treatment.

Language: Английский

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Targeting DNA Damage Response in Prostate and Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(21), P. 8273 - 8273

Published: Nov. 4, 2020

Steroid hormone signaling induces vast gene expression programs which necessitate the local formation of transcription factories at regulatory regions and large-scale alterations genome architecture to allow communication among distantly related cis-acting regions. This involves major stress genomic DNA level. Transcriptionally active are generally instable prone breakage due torsional depletion nucleosomes that make more accessible damaging agents. A dedicated damage response (DDR) is therefore essential maintain integrity these exposed The DDR a complex network involving sensor proteins, such as poly(ADP-ribose) polymerase 1 (PARP-1), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), ataxia–telangiectasia-mutated (ATM) ATM Rad3-related (ATR) kinase, central regulators. tight interplay between steroid receptors has been unraveled recently. Several repair factors interact with androgen estrogen support their transcriptional functions. Conversely, both directly control agents involved in DDR. Impaired also exploited by tumors acquire advantageous mutations. Cancer cells often harbor germline or somatic genes, association disease outcome treatment led intensive efforts towards identifying selective inhibitors targeting players this process. PARP-1 now approved for ovarian, breast, prostate cancer specific alterations. Additional DDR-targeting being evaluated clinical studies either single combination treatments eliciting (e.g., radiation therapy, including targeted radiotherapy, chemotherapy) addressing targets maintenance integrity. Recent preclinical findings made dysfunction hormone-dependent -independent breast presented. Importantly, anti-hormonal therapy inhibition potential enhance efficacy but still needs further investigation.

Language: Английский

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BET Proteins as Attractive Targets for Cancer Therapeutics

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(20), P. 11102 - 11102

Published: Oct. 14, 2021

Transcriptional dysregulation is a hallmark of cancer and can be an essential driver initiation progression. Loss transcriptional control cause cells to become dependent on certain regulators gene expression. Bromodomain extraterminal domain (BET) proteins are epigenetic readers that regulate the expression multiple genes involved in carcinogenesis. BET inhibitors (BETis) disrupt protein binding acetylated lysine residues chromatin suppress transcription various genes, including oncogenic factors. Phase I II clinical trials demonstrated BETis’ potential as anticancer drugs against solid tumours haematological malignancies; however, their success was limited monotherapies. Emerging treatment-associated toxicities, drug resistance lack predictive biomarkers progress. The preclinical evaluation BETis synergised with different classes compounds, DNA repair inhibitors, thus supporting further development BETis. combination PARP triggered synthetic lethality proficient homologous recombination. Mechanistic studies revealed targeted recombination pathway proteins, RAD51, BRCA1 CtIP. exact mechanism action remains poorly understood; nevertheless, these agents provide novel approach epigenome transcriptome therapy.

Language: Английский

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