Effects of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) on melanoma cell adhesion.
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.
Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
Huiwen
H
Cheng
Molly Y
MY
Mollica
Shin Hee
SH
Lee
Lei
L
Wang
Carlos A
CA
Velázquez-Martínez
Shiyong
S
Wu
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology; D001391:Azo Compounds / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000096:biosynthesis; D008545:Melanoma / Q000473:pathology*; D009288:Naproxen / Q000494:pharmacology; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D016029:Receptors, Very Late Antigen / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001391:Azo Compounds; D005353:Fibronectins; D016023:Integrins; D020030:Nitric Oxide Donors; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; C452539:diazeniumdiolate; D009569:Nitric Oxide; D009288:Naproxen; D001241:Aspirin