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Ibuprofen and Hydrogel-Released Ibuprofen in the Reduction of Inflammation-Induced Migration in Melanoma Cells

M Redpath, C M G Marques, C Dibden, A Waddon, R Lalla, S Macneil

Br J Dermatol. 2009 Jul;161(1):25-33.

PMID: 19438858

Abstract:

Background:
There is growing evidence that inflammation may exacerbate cancer metastasis and several clinical studies show that taking nonsteroidal anti-inflammatory drugs appears to reduce metastases.
Objectives:
The aims of this study were: (i) to examine the effects of ibuprofen on the major proinflammatory cytokine tumour necrosis factor (TNF)-alpha induction of migration of C8161 and HBL human melanoma cells; (ii) to develop ibuprofen-releasing hydrogels (Pluronics F127) for future topical use in reducing metastatic spread of primary melanoma; and (iii) to examine whether the actions of ibuprofen might be explained by induction of apoptosis.
Methods:
Melanoma cells were exposed to 300 U mL(-1) TNF-alpha for a 24-h period prior to making a scratch wound to which ibuprofen or ibuprofen-loaded hydrogels were then added. The effects of relevant concentrations of ibuprofen on cell viability and apoptosis were examined.
Results:
Ibuprofen at 10(-3) mol L(-1) significantly reduced TNF-alpha-stimulated migration of both cell types to that of nonstimulated cells (P < 0.001). TNF-alpha-unstimulated cell migration was not significantly affected. Cells responded similarly to SS and SR forms of ibuprofen. Cells treated with ibuprofen sodium salt-loaded hydrogels showed a significant reduction in migration when compared with unloaded hydrogels. Ibuprofen induced apoptosis in HBL cells but had no effect on C8161 melanoma cells apoptosis at concentrations that reduced migration.
Conclusions:
These results demonstrate that TNF-alpha upregulated malignant melanoma migration in vitro and that this could be reduced by ibuprofen both in solution and delivered from a hydrogel. These effects of ibuprofen cannot be attributed simply to induction of apoptosis.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP31121934 Ibuprofen sodium salt Ibuprofen sodium salt 31121-93-4 Price
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