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• W2079101776 abstract "Background and purpose: Angiogenesis involves multiple signaling pathways that must be considered when developing agents to modulate pathological angiogenesis. Because both cyclooxygenase inhibitors and dithioles have demonstrated anti-angiogenic properties, we investigated the activities of a new class of anti-inflammatory drugs containing dithiolethione moieties (S-NSAIDs) and S-valproate. Experimental approach: Anti-angiogenic activities of S-NSAIDS, S-valproate, and the respective parent compounds were assessed using umbilical vein endothelial cells, muscle and tumor tissue explant angiogenesis assays, and developmental angiogenesis in Fli:EGFP transgenic zebrafish embryos. Key results: Dithiolethione derivatives of diclofenac, valproate, and sulindac inhibited endothelial cell proliferation and induced Ser78 phosphorylation of hsp27, a known molecular target of anti-angiogenic signaling. The parent drugs lacked this activity, but dithiolethiones were active at comparable concentrations. Although dithiolethiones can potentially release hydrogen sulphide, NaSH did not reproduce some activities of the S-NSAIDs, indicating that the dithioles regulate angiogenesis through mechanisms other than release of H2S. In contrast to the parent drugs, S-NSAIDs, S-valproate, NaSH, and dithiolethiones were potent inhibitors of angiogenic responses in muscle and HT29 tumor explants assessed by 3-dimensional collagen matrix assays. Dithiolethiones and valproic acid were also potent inhibitors of developmental angiogenesis in zebrafish embryos, but the S-NSAIDs, remarkably, lacked this activity. Conclusions and implication: S-NSAIDs and S-valproate have potent anti-angiogenic activities mediated by their dithiole moieties. The novel properties of S-NSAIDs and S-valproate to inhibit pathological versus developmental angiogenesis suggest that these agents may have a role in cancer treatment. British Journal of Pharmacology (2007) 151, 142–151. doi:10.1038/sj.bjp.0707198" @default.
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• W2079101776 date "2007-05-01" @default.
• W2079101776 modified "2023-10-13" @default.
• W2079101776 title "Modulation of angiogenesis by dithiolethione-modified NSAIDs and valproic acid" @default.
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• W2079101776 doi "https://doi.org/10.1038/sj.bjp.0707198" @default.
• W2079101776 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2012973" @default.
• W2079101776 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17351657" @default.
• W2079101776 hasPublicationYear "2007" @default.
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