Activation of the BRCA1/Chk1/p53/p21Cip1/Waf1 pathway by nitric oxide and cell cycle arrest in human neuroblastoma NB69 cells

Wouwer, Marlies Van de; Couzinié, Célia; Serrano-Palero, Miguel; González-Fernández, Óscar; Galmés-Varela, Clara; Menéndez-Antolí, Paula; Grau, Laura; Villalobo, Antonio

doi:10.1016/j.niox.2012.02.003

Cited by 21 publications

(11 citation statements)

References 54 publications

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“…Indeed, NO has been shown to negatively regulate the proliferation of human neuroblastoma cell lines by decreasing the expression of the oncogene c-Myc in a cGMP-dependent manner (Ciani et al, 2004). Moreover, NO can inhibit the proliferation of a human neuroblastoma cancer cell line in vitro by upregulating tumor suppressor pathways, including the BRCA1/Chk1/p53 pathway, leading to cell cycle arrest in response to DNA damage via activation of cell cycle checkpoints (Van de Wouwer et al, 2012). Of note, the dual roles of NO in cancer are also dose-dependent; while exogenous NO stimulated cell proliferation in pheochromocytoma PC12 cells at low concentrations, it inhibited proliferation at higher concentrations (Bal-Price et al, 2006).…”

Section: Dichotomous Roles Of No In Cancermentioning

confidence: 99%

Arginine and the metabolic regulation of nitric oxide synthesis in cancer

Keshet

Erez

2018

Disease Models &Amp; Mechanisms

110

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Nitric oxide (NO) is a signaling molecule that plays important roles in diverse biological processes and thus its dysregulation is involved in the pathogenesis of various disorders. In cancer, NO has broad and sometimes dichotomous roles; it is involved in cancer initiation and progression, but also restricts cancer proliferation and invasion, and contributes to the anti-tumor immune response. The importance of NO in a range of cellular processes is exemplified by its tight spatial and dosage control at multiple levels, including via its transcriptional, post-translational and metabolic regulation. In this Review, we focus on the regulation of NO via the synthesis and availability of its precursor, arginine, and discuss the implications of this metabolic regulation for cancer biology and therapy. Despite the established contribution of NO to cancer pathogenesis, the implementation of NO-related cancer therapeutics remains limited, likely due to the challenge of targeting and inducing its protective functions in a cell- and dosage-specific manner. A better understanding of how arginine regulates the production of NO in cancer might thus support the development of anti-cancer drugs that target this key metabolic pathway, and other metabolic pathways involved in NO production.

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Section: Dichotomous Roles Of No In Cancermentioning

confidence: 99%

Arginine and the metabolic regulation of nitric oxide synthesis in cancer

Keshet

Erez

2018

Disease Models &Amp; Mechanisms

110

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“…Low concentrations of NO donors promote cancer progression by the activation of several mitogenic pathways, including extracellular signal-regulated kinase mTOR and Wnt/β-catenin pathways [11,12,21]. Higher doses of NO donors negatively regulate the proliferation of cancer cells by attenuating the expression of oncogenes and by the upregulation of tumor suppressors (BRCA1/Chk1/p53) culminating in cell cycle arrest via the activation of cell cycle checkpoints [14].…”

Section: Discussionmentioning

confidence: 99%

“…These results show that DETA/NO arrested cancer cells in the G1 phase. Van de Wouwer et al [14] observed that short- and long-lived NO donors inhibited the proliferation of human neuroblastoma NB69 cells by controlling G1/S transition via transcriptional repressors pRb and cyclin D1 and also by down-regulating systems regulating the S and G2/M phases. Consistent with these results, sodium nitroprusside (SNP), a NO donor, is shown to cause G0/G1 arrest in HepG2 cells [22].…”

Section: Discussionmentioning

confidence: 99%

“…Contrary to the tumorigenic promoting role, NO displays an anti-cancer role by censoring oncogenic or by stimulating tumor attenuating pathways. NO has been shown to inhibit the growth of human neuroblastoma cells by diminishing the expression of the c-Myc [13] and by enhancing the expression of tumor suppressor BRCA1/Chk1/p53 pathway, leading to cell cycle arrest [14]. Importantly, low concentrations of NO stimulated cell proliferation in cancer cells by inhibiting apoptosis, while higher concentrations inhibited proliferation by enhancing apoptosis [4,15,16].…”

Section: Introductionmentioning

confidence: 99%

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Nitric Oxide Donor DETA/NO Inhibits the Growth of Endometrial Cancer Cells by Upregulating the Expression of RASSF1 and CDKN1A

et al. 2019

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Nitric oxide (NO) is implicated in several biological processes, including cancer progression. At low concentrations, it promotes cell survival and tumor progression, and at high concentrations it causes apoptosis and cell death. Until now, the impact of NO donors has not been investigated on human endometrial tumors. Four cancer cell lines were exposed to different concentrations of DETA/NO for 24 to 120 h. The effects of DETA/NO on cell proliferation and invasion were determined utilizing MTS and Boyden chamber assays, respectively. The DETA/NO induced a dose and time-dependent reduction in cell viability by the activation of caspase-3 and cell cycle arrest at the G0/G1 phase that was associated with the attenuated expression of cyclin-D1 and D3. Furthermore, the reduction in the amount of CD133-expressing cancer stem-like cell subpopulation was observed following DETA/NO treatment of cells, which was associated with a decreased expression of stem cell markers and attenuation of cell invasiveness. To understand the mechanisms by which DETA/NO elicits anti-cancer effects, RNA sequencing (RNA-seq) was used to ascertain alterations in the transcriptomes of human endometrial cancer cells. RNA-seq analysis revealed that 14 of the top 21 differentially expressed genes were upregulated and seven were downregulated in endometrial cancer cells with DETA/NO. The genes that were upregulated in all four cell lines with DETA/NO were the tumor suppressors Ras association domain family 1 isoform A (RASSF1) and Cyclin-dependent kinase inhibitor 1A (CDKN1A). The expression patterns of these genes were confirmed by Western blotting. Taken together, the results provide the first evidence in support of the anti-cancer effects of DETA/NO in endometrial cancer.

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“…One proposed mechanism for the anticancer effects of NO is through the upregulation of a pathway involving BRCA1, Chk1, p53, and p21. This pathway is involved in controlling the cell cycle and can cause cell cycle arrest and cell death in response to DNA damage or other types of cellular stress [ 76 ].…”

Section: Clinical Use Against Cancermentioning

confidence: 99%

Repurposing of the Drug Tezosentan for Cancer Therapy

Ribeiro

Vale

2023

CIMB

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Tezosentan is a vasodilator drug that was originally developed to treat pulmonary arterial hypertension. It acts by inhibiting endothelin (ET) receptors, which are overexpressed in many types of cancer cells. Endothelin-1 (ET1) is a substance produced by the body that causes blood vessels to narrow. Tezosentan has affinity for both ETA and ETB receptors. By blocking the effects of ET1, tezosentan can help to dilate blood vessels, improve the blood flow, and reduce the workload on the heart. Tezosentan has been found to have anticancer properties due to its ability to target the ET receptors, which are involved in promoting cellular processes such as proliferation, survival, neovascularization, immune cell response, and drug resistance. This review intends to demonstrate the potential of this drug in the field of oncology. Drug repurposing can be an excellent way to improve the known profiles of first-line drugs and to solve several resistance problems of these same antineoplastic drugs.

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Activation of the BRCA1/Chk1/p53/p21Cip1/Waf1 pathway by nitric oxide and cell cycle arrest in human neuroblastoma NB69 cells

Cited by 21 publications

References 54 publications

Arginine and the metabolic regulation of nitric oxide synthesis in cancer

Arginine and the metabolic regulation of nitric oxide synthesis in cancer

Nitric Oxide Donor DETA/NO Inhibits the Growth of Endometrial Cancer Cells by Upregulating the Expression of RASSF1 and CDKN1A

Repurposing of the Drug Tezosentan for Cancer Therapy

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