High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

Liu, Ying; Yu, Zhuang; Zhao, Ying; Gao, Dongna; Xing, Jing; Liu, Hui

doi:10.3892/ol.2016.5169

Cited by 54 publications

(48 citation statements)

References 53 publications

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“…PARP1, an ADP‐ribosylating enzyme, participates in repair of various forms DNA damage and maintains chromatin remodeling . Overexpression of PARP1 has been found in high stage cancers . Liu et al presented PARP1 inhibitor not only induces DNA double‐strand breaks (DSB) but also sensitizes bladder cancer cells to radiation.…”

Section: Discussionmentioning

confidence: 99%

“…25 Overexpression of PARP1 has been found in high stage cancers. 26,27 Liu et al 28 presented PARP1 inhibitor not only induces DNA double-strand breaks (DSB) but also sensitizes bladder cancer cells to radiation. We found regorafenib significantly induces apoptosis and increases activation of Fas/FasL, Caspase-8, -3, loss of ΔΨm, and cleavage of PARP1 in bladder cancer TSGH 8301 cells.…”

Section: Discussionmentioning

confidence: 99%

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Regorefenib induces extrinsic/intrinsic apoptosis and inhibits MAPK/NF‐κB‐modulated tumor progression in bladder cancer in vitro and in vivo

Chiang

Chung

Hsu

2019

Environmental Toxicology

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The aim of the present study is to investigate anticancer effect and mechanism of regorafenib in bladder cancer in vitro and in vivo . Human bladder cancer TSGH 8301 cells were treated with regorafenib, NF‐κB, AKT, or mitogen‐activated protein kinase (MAPK) inhibitors for different time. The changes of cell viability, NF‐κB activation, apoptotic signaling transduction, and expression of tumor progression‐associated proteins were evaluated with MTT, NF‐κB reporter gene assay, flow cytometry, and Western blotting assay. TSGH 8301 tumor bearing mice were established and treated with vehicle (140 μL of 0.1% DMSO) or regorafenib (10 mg/kg/day by gavage) for 15 days. The changes of tumor volume, body weight, NF‐κB activation, MAPK activation, and tumor progression‐associated proteins (MMP‐9, XIAP, VEGF, and Cyclin‐D1) after regorafenib treatment were evaluated with digital caliper, digital weight, and ex vivo Western blotting assay. Our results demonstrated NF‐κB activation and protein levels of MMP‐9, XIAP, VEGF, and Cyclin‐D1 were significantly reduced by NF‐κB (QNZ), ERK (PD98059), and P38 (SB203580) inhibitors. Regorafenib also significantly induced extrinsic and intrinsic apoptotic signaling transduction in bladder cancer in vitro . In addition, regorafenib significantly inhibited tumor growth, NF‐κB, p38, ERK activation and expression of tumor progression‐associated proteins in bladder cancer in vitro and in vivo . Taken together, these results proved that regorafenib not only induced apoptosis through extrinsic and intrinsic pathways and but suppressed MAPK/ NF‐κB‐modulated tumor progression in bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Regorefenib induces extrinsic/intrinsic apoptosis and inhibits MAPK/NF‐κB‐modulated tumor progression in bladder cancer in vitro and in vivo

Chiang

Chung

Hsu

2019

Environmental Toxicology

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“…The Helicobacter pylori infection significantly induced PARP1 activation . Thus, H. pylori infected gastric cancer cells and metastasized cells have higher PARP1 expression, suggesting the involvement of PARP1 in progression of gastric cancer and its poor prognosis . PARP1 in gastric cancer leads to the activation of antiproliferating transcription factor FOXO3A via AKT activity.…”

Section: Functional Role Of Parp1 In Various Cancersmentioning

confidence: 99%

“…74 Thus, H. pylori infected gastric cancer cells and metastasized cells have higher PARP1 expression, suggesting the involvement of PARP1 in progression of gastric cancer and its poor prognosis. 75…”

Section: H Parp1 In Gastric Cancermentioning

confidence: 99%

Therapeutic Targeting of Poly(ADP‐Ribose) Polymerase‐1 (PARP1) in Cancer: Current Developments, Therapeutic Strategies, and Future Opportunities

Rajawat

Shukla

Mishra

2017

Medicinal Research Reviews

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Poly(ADP-ribose) polymerase-1 (PARP-1) plays a central role in numerous cellular processes including DNA repair, replication, and transcription. PARP interacts directly, indirectly or via PARylation with various oncogenic proteins and regulates several transcription factors thereby modulating carcinogenesis. Therapeutic inhibition of PARP is therefore perceived as a promising anticancer strategy and a number of PARP inhibitors (PARPi) are currently under development and clinical evaluation. PARPi inhibit the DNA repair pathway and thus form the concept of synthetic lethality in cancer therapeutics. Preclinical and clinical studies have shown the potential of PARPi as chemopotentiator, radiosensitizer, or as adjuvant therapeutic agents. Recent studies have shown that PARP-1 could be either oncogenic or tumor suppressive in different cancers. PARP inhibitor resistance is also a growing concern in the clinical setting. Recently, changes in the levels of PARP-1 activity or expression in cancer patients have provided the basis for consideration of PARP-1 regulatory proteins as potential biomarkers. This review focuses on the current developments related to the role of PARP in cancer progression, therapeutic strategies targeting PARP-associated oncogenic signaling, and future opportunities in use of PARPi in anticancer therapeutics.

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“…[5][6][7][8][9][10] High PARP1 expression also promotes tumor invasion or metastasis, contributing to the poor prognosis of patients with various types of solid tumors. [11][12][13] PARP1 also modulates the sensitivity of tumor cells to drugs such as cisplatin 14 and decitabine. 15 Thus, high expression of PARP1 may contribute to tumorigenesis in several solid tumors.…”

Section: Introductionmentioning

confidence: 99%

PARP1 V762A polymorphism affects the prognosis of myelodysplastic syndromes

Gotoh

Minato

Saitoh

et al. 2020

European J of Haematology

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Objective: Myelodysplastic syndromes (MDS), caused by various genetic mutations in hematopoietic stem cells, are associated with highly variable outcomes. Poly (ADP-ribose) polymerase-1 (PARP1) plays an important role in DNA damage repair and contributes to the progression of several types of cancer. Here, we investigated the impact of PARP1 V762A polymorphism on the susceptibility to and prognosis of MDS.Methods: Samples collected from 105 MDS patients and 202 race-matched healthy controls were subjected to polymerase chain reaction-restriction fragment length polymorphism for genotyping. Results:The allele and genotype frequencies of PARP1 V762A did not differ between MDS patients and the control group. However, MDS patients with the PARP1 V762A non-AA genotype, which is associated with high gene activity, had shorter overall survival rates (P = .01) than those with the AA genotype. Multivariate analysis of overall survival also revealed PARP1 V762A non-AA genotype as a poor prognostic factor (P = .02). When patients were analyzed according to treatment history, the PARP1 V762A non-AA genotype was only associated with poor survival in patients who had received treatment (P = .02).Conclusion: PARP1 V762A polymorphism may be an independent prognostic factor for MDS, and a predictive biomarker for MDS treatment. K E Y W O R D S myelodysplastic syndromes, PARP1, polymorphism | 527 GOTOH eT al.

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High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

Cited by 54 publications

References 53 publications

Regorefenib induces extrinsic/intrinsic apoptosis and inhibits MAPK/NF‐κB‐modulated tumor progression in bladder cancer in vitro and in vivo

Regorefenib induces extrinsic/intrinsic apoptosis and inhibits MAPK/NF‐κB‐modulated tumor progression in bladder cancer in vitro and in vivo

Therapeutic Targeting of Poly(ADP‐Ribose) Polymerase‐1 (PARP1) in Cancer: Current Developments, Therapeutic Strategies, and Future Opportunities

PARP1 V762A polymorphism affects the prognosis of myelodysplastic syndromes

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