The multi-factorial nature of clinical multidrug resistance in cancer

Drug Resistance Updates, Год журнала: 2019, Номер 46, С. 100645 - 100645

Опубликована: Сен. 1, 2019

Язык: Английский

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Poly(ADP-ribose) polymerase inhibition: past, present and future

Nature Reviews Drug Discovery, Год журнала: 2020, Номер 19(10), С. 711 - 736

Опубликована: Сен. 3, 2020

Язык: Английский

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Multifaceted Role of PARP-1 in DNA Repair and Inflammation: Pathological and Therapeutic Implications in Cancer and Non-Cancer Diseases

Cells, Год журнала: 2019, Номер 9(1), С. 41 - 41

Опубликована: Дек. 22, 2019

PARP-1 (poly(ADP-ribose)-polymerase 1), mainly known for its protective role in DNA repair, also regulates inflammatory processes. Notably, defects repair and chronic inflammation may both predispose to cancer development. On the other hand, inhibition of responses can be beneficial therapy PARP inhibitors are currently used their lethal effects on tumor cells. Furthermore, excess activity has been associated with many tumors inflammation-related clinical conditions, including asthma, sepsis, arthritis, atherosclerosis, neurodegenerative diseases, name a few. Activation represent, therefore, double-edged sword that exploited therapeutic purposes. In our review, we will discuss recent findings highlighting composite multifaceted diseases.

Язык: Английский

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Imidazoles as Potential Anticancer Agents: An Update on Recent Studies

Molecules, Год журнала: 2021, Номер 26(14), С. 4213 - 4213

Опубликована: Июль 11, 2021

Nitrogen-containing heterocyclic rings are common structural components of marketed drugs. Among these heterocycles, imidazole/fused imidazole present in a wide range bioactive compounds. The unique properties such structures, including high polarity and the ability to participate hydrogen bonding coordination chemistry, allow them interact with biomolecules, imidazole-/fused imidazole-containing compounds reported have broad spectrum biological activities. This review summarizes recent reports derivatives as anticancer agents appearing peer-reviewed literature from 2018 through 2020. Such molecules been shown modulate various targets, microtubules, tyrosine serine-threonine kinases, histone deacetylases, p53-Murine Double Minute 2 (MDM2) protein, poly (ADP-ribose) polymerase (PARP), G-quadraplexes, other targets. Imidazole-containing that display activity by unknown/undefined mechanisms also described, well key features structure-activity relationships. is intended provide an overview advances imidazole-based drug discovery development, inspire design synthesis new molecules.

Язык: Английский

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Long non-coding RNA GAS5 inhibits DDP-resistance and tumor progression of epithelial ovarian cancer via GAS5-E2F4-PARP1-MAPK axis

Journal of Experimental & Clinical Cancer Research, Год журнала: 2019, Номер 38(1)

Опубликована: Авг. 7, 2019

Epithelial ovarian cancer (EOC) is the malignant tumor of female reproductive system with highest fatality rate. Tolerance chemotherapeutic drugs like cisplatin (DDP) occurring in very early stage one important factors poor prognosis epithelial cancer. Here we aim to study dysregulation a particular long noncoding RNA, lncRNA GAS5, and its role EOC progression.The low expression GAS5 tissues OC cell lines was determined by microarray analyses Real-Time qPCR. Flow cytometer assays were used detect cycle apoptosis cells. CCK8 assay performed investigate DDP sensitivity Western blot carried out growth markers, apoptotic PARP1, E2F4, MAPK pathway protein other lines. The binding E2F4 proved RNA pull-down RIP assay. effect on PARP1 CHIP-qPCR luciferase reporter cells assessed vitro vivo.By (3 νs. 3 normal ovary tissues) RT- qPCR (53 10 identified be dramatically expressed samples correlated prognosis. Compared sensitive lines, also resistant over-expression significantly enhanced vivo vitro. Meanwhile caused G0/G1 arrest increase. Mechanistically, might regulate recruiting transcription factor promoter, then affect activity. Due 5'TOP structure, could regulated inhibitor rapamycin cells.Here explored specific mechanisms resistance progress due lncRNA-GAS5, presented GAS5-E2F4-PARP1-MAPK axis drug-sensitivity progression for first time, results may provide experimental basis clinical application.

Язык: Английский

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The involvement of stress granules in aging and aging‐associated diseases

Aging Cell, Год журнала: 2020, Номер 19(4)

Опубликована: Март 14, 2020

Abstract Stress granules (SGs) are nonmembrane assemblies formed in cells response to stress conditions. SGs mainly contain untranslated mRNA and a variety of proteins. RNAs scaffold proteins with intrinsically disordered regions or RNA‐binding domains essential for the assembly SGs, multivalent macromolecular interactions among these components thought be driving forces SG assembly. The process includes regulation through post‐translational modification involvement cytoskeletal system. During aging, many intracellular bioprocesses become disrupted by factors such as cellular environmental changes, mitochondrial dysfunction, decline protein quality control Such changes could lead formation aberrant well alterations their maintenance, disassembly, clearance. These might turn promote aging aging‐associated diseases. In this paper, we first review latest progress on molecular mechanisms underlying functioning under Then, provide detailed discussion relevance

Язык: Английский

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HPF1 remodels the active site of PARP1 to enable the serine ADP-ribosylation of histones

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Фев. 15, 2021

Upon binding to DNA breaks, poly(ADP-ribose) polymerase 1 (PARP1) ADP-ribosylates itself and other factors initiate repair. Serine is the major residue for ADP-ribosylation upon damage, which strictly depends on HPF1. Here, we report crystal structures of human HPF1/PARP1-CAT ΔHD complex at 1.98 Å resolution, mouse HPF1 1.71 1.57 respectively. Our mutagenesis data confirm that structural insights obtained in a recent HPF1/PARP2 study by Suskiewicz et al. apply PARP1. Moreover, quantitatively characterize key residues necessary HPF1/PARP1 binding. show through salt-bridging Glu284/Asp286, Arg239 positions Glu284 catalyze serine ADP-ribosylation, maintains local conformation limit PARP1 automodification, facilitates neutralizing negative charge Glu284. These findings, along with high-resolution data, may facilitate drug discovery targeting

Язык: Английский

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Adverse Event Profiles of PARP Inhibitors: Analysis of Spontaneous Reports Submitted to FAERS

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Март 25, 2022

Background: Several poly ADP ribose polymerase inhibitors (PARPis) are currently approved for the treatment of a variety cancers. The safety profile PARPis has not yet been systemically analyzed in real world. We conducted this pharmacovigilance analysis using US FDA's Adverse Event Reporting System (FAERS) database to explore difference adverse events (AEs) among PARPis. Methods: FAERS data (December 2014 October 2021) were searched reports all FDA-approved across indications. used standardized MedDRA query (SMQ) generalized search AEs on preferred term (PT) level based case reports. After filtering duplicate reports, disproportionality was detect signals by calculating reporting odds ratios (ROR). Reports considered statistically significant if 95% confidence interval did contain null value. Results: Within queries, found, including those olaparib [blood premalignant disorders (ROR = 17.06)], rucaparib [taste and smell 9.17)], niraparib [hematopoietic throbocytopenia 28.2)], talazoparib erythropenia 9.38)]. For PT level, we found several signals, platelet count decreased with 52.78); red blood cell 70.47) 15.09); myelodysplastic syndrome 35.47); acute myeloid leukaemia 25.14); pressure fluctuation 20.54); lymphangioleiomyomatosis 471.20); photosensitivity reaction 21.77) 18.92); renal impairment 33.32); interstitial lung disease Olaparib 11.31). All detected confirmed methods. Conclusion: differed their revealed that matched previously published serious gastrointestinal, lymphatic system, cardiovascular respiratory complications, which require individualized drug administration according patients' conditions.

Язык: Английский

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A review of poly(ADP-ribose)polymerase-1 (PARP1) role and its inhibitors bearing pyrazole or indazole core for cancer therapy

Biochemical Pharmacology, Год журнала: 2024, Номер 221, С. 116045 - 116045

Опубликована: Фев. 8, 2024

Cancer is a disease with high mortality rate characterized by uncontrolled proliferation of abnormal cells. The hallmarks cancer evidence the acquired cells characteristics that promote growth malignant tumours, including genomic instability and mutations, ability to evade cellular death capacity sustaining proliferative signalization. Poly(ADP-ribose) polymerase-1 (PARP1) protein plays key roles in regulation, namely DNA damage repair cell survival. inhibition PARP1 promotes homologous recombination deficiency, therefore, interest PARP has been rising as target for anticancer therapies. There are already some inhibitors approved Food Drug Administration (FDA), such Olaparib Niraparib. last compound presents its structure an indazole core. In fact, pyrazoles indazoles have raising due their various medicinal properties, namely, activity. Derivatives these compounds studied presented promising results. Therefore, this review aims address importance regulation role cancer. Moreover, it intends report comprehensive literature inhibitors, containing pyrazole scaffolds, published fifteen years, focusing on structure-activity relationship aspects, thus providing important insights design novel more effective inhibitors.

Язык: Английский

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A bioactive fraction from the leaves of Ceiba pentandra (L.) Gaertn. exhibits antiproliferative activity via cell cycle arrest at the G1/S checkpoint and initiation of apoptosis via poly [ADP-ribose] polymerase 1 (PARP1) cleavage in HeLa cells.

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119363 - 119363

Опубликована: Янв. 1, 2025

Язык: Английский

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