The beneficial effects of H2S-release and of COXs-inhibition have been exploited in the design of novel anti-inflammatory drugs, the H2S-releasing non-steroidal anti-inflammatory drugs (H2S-NSAIDs), showing promising potential for chemoprevention in cancers. Here, we evaluated the efficacy of a new H2S-releasing derivative of naproxen, named naproxen-4-hydroxybenzodithioate (naproxen-HBTA), in reducing metastatic melanoma features, both in vitro and in vivo. The novel H2S donor has been prepared following a synthetic scheme that provided high yields and purity. In particular, we investigated the effect of naproxen-HBTA in vitro on several metastatic features of human melanoma cells such as proliferation, migration, invasion, and colonies formation and in vivo 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 H2S pathways could be regarded as novel therapeutic targets/tools to generate new treatment options based on "combination therapy" for melanoma.

Anti-metastatic properties of naproxen-HBTA in a murine model of cutaneous melanoma / Ercolano, G.; De Cicco, P.; Frecentese, F.; Saccone, I.; Corvino, A.; Giordano, F.; Magli, E.; Fiorino, F.; Severino, B.; Calderone, V.; Citi, V.; Cirino, G.; Ianaro, A.. - In: FRONTIERS IN PHARMACOLOGY. - ISSN 1663-9812. - 10:(2019), p. 66. [10.3389/fphar.2019.00066]

Anti-metastatic properties of naproxen-HBTA in a murine model of cutaneous melanoma

Ercolano G.;De Cicco P.;Frecentese F.;Saccone I.;Corvino A.;Giordano F.;Magli E.;Fiorino F.;Severino B.;Cirino G.;Ianaro A.
2019

Abstract

The beneficial effects of H2S-release and of COXs-inhibition have been exploited in the design of novel anti-inflammatory drugs, the H2S-releasing non-steroidal anti-inflammatory drugs (H2S-NSAIDs), showing promising potential for chemoprevention in cancers. Here, we evaluated the efficacy of a new H2S-releasing derivative of naproxen, named naproxen-4-hydroxybenzodithioate (naproxen-HBTA), in reducing metastatic melanoma features, both in vitro and in vivo. The novel H2S donor has been prepared following a synthetic scheme that provided high yields and purity. In particular, we investigated the effect of naproxen-HBTA in vitro on several metastatic features of human melanoma cells such as proliferation, migration, invasion, and colonies formation and in vivo 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 H2S pathways could be regarded as novel therapeutic targets/tools to generate new treatment options based on "combination therapy" for melanoma.
2019
Anti-metastatic properties of naproxen-HBTA in a murine model of cutaneous melanoma / Ercolano, G.; De Cicco, P.; Frecentese, F.; Saccone, I.; Corvino, A.; Giordano, F.; Magli, E.; Fiorino, F.; Severino, B.; Calderone, V.; Citi, V.; Cirino, G.; Ianaro, A.. - In: FRONTIERS IN PHARMACOLOGY. - ISSN 1663-9812. - 10:(2019), p. 66. [10.3389/fphar.2019.00066]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/772302
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