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

• Published in: Frontiers 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
• Language: English
• Published: Switzerland Frontiers Media S.A 08.02.2019
• Subjects: apoptosis; cyclooxygenases (COXs); hydrogen sulfide (H2S); melanoma; non-steroidal anti-inflammatory drugs (NSAIDs); Pharmacology; target-therapy; non-steroidal anti-inflammatory drugs (NSAIDs); apoptosis; melanoma; target-therapy; hydrogen sulfide (H2S); cyclooxygenases (COXs)
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2019.00066

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.