Effects of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) on melanoma cell adhesion
- Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States)
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 β1 integrin, which binds to α4 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. -- Highlights: ► NONO-naproxen, a novel nitric oxide-releasing NSAID, was synthesized. ► NONO-NSAIDs, but not their parent NSAIDs, reduced melanoma adhesion. ► NONO-naproxen, but not NONO-aspirin and NSAIDs, reduced activity of β1 integrin.
- OSTI ID:
- 22215935
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 264, Issue 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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