Dataset Information

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

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.

SUBMITTER: Ercolano G

PROVIDER: S-EPMC6376415 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Ercolano Giuseppe G De Cicco Paola P Frecentese Francesco F Saccone Irene I Corvino Angela A Giordano Flavia F Magli Elisa E Fiorino Ferdinando F Severino Beatrice B Calderone Vincenzo V Citi Valentina V Cirino Giuseppe G Ianaro Angela A

Frontiers in pharmacology 20190208

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 ...[more]

PMID: 30800067

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Project description:BackgroundThe most deadly form of cancer is not lung or colon, breast or prostate; it is any cancer that has become metastatic. Mortality due to metastatic melanoma, one of the most aggressive and deadly cancers, has increased steadily over the last several decades. Unfortunately, the arsenal of chemotherapeutic agents available today is most often unsuccessful at extending and improving the life expectancy of afflicted individuals. We sought to identify an effective and nontoxic agent against metastatic melanoma.Methodology/principal findingsWe chose to study Cloudman S-91 mouse melanoma cells (sub-clone M3, CCL53.1) because these cells are highly aggressive and metastatic, representing one of the deadliest types of cancer. Melanoma cells also had an experimental advantage because their morphology, which is easily monitored, relates to the physiology of metastatic cells and normal melanocytes. We chose to test methyl sulfone as a chemotherapeutic agent for two reasons. Because of its chemical structure, we speculated a potential anti-cancer activity by targeting microtubules. Equally important, methyl sulfone has a well-established safety profile in humans. Surprisingly, we found that malignant melanoma cells exposed to methyl sulfone demonstrated the loss of phenotypes characteristic of malignant cells, and the reemergence of phenotypes characteristic of healthy melanocytes. Briefly, over time methyl sulfone induced contact inhibition, loss of ability to migrate through an extracellular matrix, loss of anchorage-independent growth, proper wound healing followed by contact inhibition, irreversible senescence followed by arborization with melanosomes in arbors as seen in normal melanocytes.Conclusions/significanceMethyl sulfone may have clinical potential as a non-toxic agent effective against metastatic melanoma. Additionally, methyl sulfone has promise as a tool to explore molecular mechanisms of metastatic transformation as well as fundamental processes such as cell migration, contact inhibition, wound healing and cellular senescence.

Dataset Information

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

Publications

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

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