Anti-metastatic Properties of Naproxen-HBTA in a Murine Model of Cutaneous Melanoma

The beneficial effects of H S-release and of COXs-inhibition have been exploited in the design of novel anti-inflammatory drugs, the H S-releasing non-steroidal anti-inflammatory drugs (H S-NSAIDs), showing promising potential for chemoprevention in cancers. Here, we evaluated the efficacy of a new...

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Published inFrontiers in pharmacology Vol. 10; p. 66
Main Authors Ercolano, Giuseppe, De Cicco, Paola, Frecentese, Francesco, Saccone, Irene, Corvino, Angela, Giordano, Flavia, Magli, Elisa, Fiorino, Ferdinando, Severino, Beatrice, Calderone, Vincenzo, Citi, Valentina, Cirino, Giuseppe, Ianaro, Angela
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 08.02.2019
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Summary:The beneficial effects of H S-release and of COXs-inhibition have been exploited in the design of novel anti-inflammatory drugs, the H S-releasing non-steroidal anti-inflammatory drugs (H S-NSAIDs), showing promising potential for chemoprevention in cancers. Here, we evaluated the efficacy of a new H S-releasing derivative of naproxen, named naproxen-4-hydroxybenzodithioate (naproxen-HBTA), in reducing metastatic melanoma features, both and . The novel H S donor has been prepared following a synthetic scheme that provided high yields and purity. In particular, we investigated the effect of naproxen-HBTA on several metastatic features of human melanoma cells such as proliferation, migration, invasion, and colonies formation and in a model of cutaneous melanoma. Cell culture studies demonstrated that naproxen-HBTA induced caspase 3-mediated apoptosis and inhibited motility, invasiveness, and focus formation. Finally, daily oral treatment with naproxen-HBTA significantly suppressed melanoma growth and progression in mice. In conclusion, by using this dual approach we propose that the COX-2 and H S pathways could be regarded as novel therapeutic targets/tools to generate new treatment options based on "combination therapy" for melanoma.
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Reviewed by: Carlos Rogerio De Figueiredo, University of Liverpool, United Kingdom; Stefano Fiorucci, University of Perugia, Italy
These authors have contributed equally to this work
This article was submitted to Pharmacology of Anti-Cancer Drugs, a section of the journal Frontiers in Pharmacology
Edited by: Simona Rapposelli, University of Pisa, Italy
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2019.00066