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

Frontiers in Pharmacology
Giuseppe ErcolanoAngela Ianaro

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 ...Continue Reading

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Citations

May 6, 2019·British Journal of Pharmacology·Silvia A Coavoy-SánchezMarcelo N Muscará
Oct 8, 2019·Antioxidants & Redox Signaling·Alma MartelliVincenzo Calderone
May 6, 2020·Mini Reviews in Medicinal Chemistry·M İhsan Han, Ş Güniz Küçükgüzel
Dec 2, 2020·Expert Opinion on Drug Discovery·Alma MartelliVincenzo Calderone
Apr 4, 2021·Antioxidants·Angela CorvinoBeatrice Severino
May 15, 2021·Oxidative Medicine and Cellular Longevity·Qing XiaoLi Li

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Methods Mentioned

BETA
scraping
column chromatography
FACS

Software Mentioned

ARRIVE
CellQuest
GraphPad
Image
Image J
GrapdPad Prism
GraphPad Prism

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