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Effects of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) on melanoma cell adhesion.

ABSTRACT: A new class of nitric oxide (NO•)-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) were developed in recent years and have shown promising potential as NSAID substitutes due to their gentle nature on cardiovascular and gastrointestinal systems. Since nitric oxide plays a role in regulation of cell adhesion, we assessed the potential use of NONO-NSAIDs as anti-metastasis drugs. In this regard, we compared the effects of NONO-aspirin and a novel NONO-naproxen to those exerted by their respective parent NSAIDs on avidities of human melanoma M624 cells. Both NONO-NSAIDs, but not the corresponding parent NSAIDs, reduced M624 adhesion on vascular cellular adhesion molecule-1 (VCAM-1) by 20-30% and fibronectin by 25-44% under fluid flow conditions and static conditions, respectively. Only NONO-naproxen reduced (~56%) the activity of ?1 integrin, which binds to ?4 integrin to form very late antigen-4 (VLA-4), the ligand of VCAM-1. These results indicate that the diazeniumdiolate (NO•)-donor moiety is critical for reducing the adhesion between VLA-4 and its ligands, while the NSAID moiety can impact the regulation mechanism of melanoma cell adhesion.

SUBMITTER: Cheng H

PROVIDER: S-EPMC3462299 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Effects of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) on melanoma cell adhesion.

Cheng Huiwen H Mollica Molly Y MY Lee Shin Hee SH Wang Lei L Velázquez-Martínez Carlos A CA Wu Shiyong S

Toxicology and applied pharmacology 20120804 2

A new class of nitric oxide (NO•)-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) were developed in recent years and have shown promising potential as NSAID substitutes due to their gentle nature on cardiovascular and gastrointestinal systems. Since nitric oxide plays a role in regulation of cell adhesion, we assessed the potential use of NONO-NSAIDs as anti-metastasis drugs. In this regard, we compared the effects of NONO-aspirin and a novel NONO-naproxen to those exerted by their ...[more]

PMID: 22889880

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Project description:ObjectivesPotentially harmful nonsteroidal anti-inflammatory drugs (NSAIDs) utilization persists at undesirable rates throughout the world. The purpose of this paper is to review the literature on interventions to de-implement potentially harmful NSAIDs in healthcare settings and to suggest directions for future research.DesignScoping review.Data sourcesPubMed, CINAHL, Embase, Cochrane Central, and Google Scholar (2000-2022).Study selectionStudies reporting on the effectiveness of interventions to systematically reduce potentially harmful NSAID utilization in healthcare settings.Data extractionUsing Covidence systematic review software, we extracted study and intervention characteristics, including the effectiveness of interventions in reducing NSAID utilization.ResultsFrom 7,818 articles initially identified, 68 were included in the review. Most studies took place in European countries (45.6%) or the U.S. (35.3%), with randomized controlled trial as the most common design (55.9%). The majority of studies (76.2%) reported a reduction in the utilization of potentially harmful NSAIDs. Interventions were largely clinician-facing (76.2%) and delivered in primary care (60.2%). Academic detailing, clinical decision support or electronic medical record interventions, performance reports, and pharmacist review were frequent approaches employed. NSAID use was most commonly classified as potentially harmful based on patients' age (55.8%) or history of gastrointestinal disorders (47.1%) or kidney disease (38.2%). Only 7.4% of interventions focused on over-the-counter NSAIDs in addition to prescription. Few studies (5.9%) evaluated pain or quality of life following NSAIDs discontinuation.ConclusionMany varied interventions are effective in de-implementing potentially harmful NSAIDs in healthcare settings. Efforts to adapt, scale, and disseminate these interventions are needed. In addition, future interventions should address over-the-counter NSAIDs, which are broadly available and widely used. Evaluating unintended consequences of interventions, including patient-focused outcomes, is another important priority. What is already known on this topic - NSAIDs are overutilized by high-risk patients at persistent rates. Interventions to reduce potentially harmful NSAIDs prescribing and over-the-counter (OTC) NSAIDs use are needed . What this study adds - More than 50 studies published internationally from 2000 to 2022 (three quarters of those reviewed) reported on interventions effective in de-implementing potentially harmful NSAIDs. We extracted and summarized characteristics of studies and of interventions to identify research gaps and priorities for future research . How this study might affect research, practice or policy - In light of the large number of effective interventions on record, implementation and dissemination efforts should be the priority of future work .

Dataset Information

Effects of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) on melanoma cell adhesion.

Publications

Effects of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) on melanoma cell adhesion.

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