Image_1_Anti-metastatic Properties of Naproxen-HBTA in a Murine Model of Cutaneous Melanoma.TIF (968.57 kB)

Image_1_Anti-metastatic Properties of Naproxen-HBTA in a Murine Model of Cutaneous Melanoma.TIF

Download (968.57 kB)
figure
posted on 26.02.2019 by Giuseppe Ercolano, Paola De Cicco, Francesco Frecentese, Irene Saccone, Angela Corvino, Flavia Giordano, Elisa Magli, Ferdinando Fiorino, Beatrice Severino, Vincenzo Calderone, Valentina Citi, Giuseppe Cirino, Angela Ianaro

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.

History

References

Licence

Exports