Nitric oxide donating non steroidal anti-inflammatory drugs (NO-NSAIDs) for the treatment of cancer.

Abstract

Nitric oxide donating non steroidal anti-inflammatory drugs (NO-NSAIDs) represent an emerging class of compounds with chemopreventive, chemotherapeutic, chemio-, radio- and immunosensitizing properties against a variety of cancers. These compounds consist of a conventional NSAID to which an NO-releasing moiety ONO2 has been covalently attached. The aim of our study was to evaluate the anticancer potential of the novel NO-NSAID naproxcinod, since it is the only NO-NSAID that, differently from other compounds belonging to the same class, has so far demonstrated a clear safe profile in humans and has not been extensively studied yet as a potential novel anticancer therapeutic. We show here that Naproxcinod is particular effective in both androgen-dependent and androgen-independent prostate cancer cells and colon cancer cells. We have further validated the results obtained in vitro in murine xenograft models. The data show a strong antitumoral effect of Naproxcinod in all of the models tested. However, Naproxcinod was not able to significantly decrease the metastatic potential of the CT26CL25 colon cancer cells to the lungs. In conclusion, these data provide strong support for the design of phase II trials based on the administration of Naproxcinod to cancer patients in association to conventional therapies or to prevent disease recurrence.