Piroxicam, from the group of the oxicams, is mainly known as a non-steroidal anti-inflammatory drug (NSAID), used in the treatment of chronic rheumatic diseases. The molecular target of NSAIDs is cyclooxygenase (COX). There are three isoforms of the enzyme (COX-1, COX-2 and COX-3).

Most solid tumors express the cyclooxygenase-2 (COX-2) protein, which is a target of NSAIDs, and that is why those drugs are evaluated as anti-cancer. They inhibit proliferation, invasiveness of tumors, and angiogenesis and overcome apoptosis resistance [1]. NSAIDs particulary decrease the incidence of and mortality from colon cancer, and therefore those drugs have been a major advance in chemoprevention [2].

Lenard Lichtenberger et al think that one of the alternative mechanisms by which NSAIDs can be effective is by interacting with cellular membranes and altering their biophysical properties. Those drugs can induce changes in the fluidity, permeability and biomechanical properties of cell membranes [3].

To optimize and modulate the biological effects of piroxicam, some efforts are made to synthesize the derivatives of this oxicam. In our present work we studied the influence of two new piroxicam analogues PR17 and PR18, synthesized in our department, on lipid bilayers.

We studied the thermal effects of these compounds in dipalmitoylphosphatidylcholine (DPPC) membrane bilayers. The addition of PR17 and PR18 to DPPC resulted in a decrease in the lipid main transition temperature and the broadening of the transition peaks.

In spectroscopic experiments we assessed the influence of the oxicams under consideration on Laurdan and Prodan (two fluorescent probes localized in different membrane segments) fluorescence in liposomes made of lecithin from egg yolk (EYPC). PR17 and PR18 quenched the fluorescence of both Laurdan and Prodan.

The results presented allow the conclusion that the studied oxicams interact with the studied lipid bilayers and may penetrate the membranes.

References:

[1] D.J.A. de Groot, E.G.E. de Vires, H.J.M. Groen, S. de Jong, Non-steroidal  anti- inflammatory drugs to potentiate chemotherapy effects: From lab to clinic, Critical Revievs in Oncology/Hematology, 61, (2007), p. 52–69;

[2] K. Gwyn, F.A. Sinicrope, Chemoprevention of Colorectal Cancer, The American Journal of Gastroenterology, vol. 97, No 1, (2002), p. 13–21;

[3] L.M. Lichtenberger, Y. Zhou, V. Jayaraman, J.R. Doyen, R.G. O'Neil, E.J. Dial, D.G. Gorenstein, M.B. Boggara, R. Krishnamoorti, Insight into NSAID-induced membrane alterations, pathogenesis and therapeutics: Characterization of interaction of NSAIDs with phosphatidylcholine, Biochimica et Biophysica Acta, 1821 (2012), p. 994–1002.

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1. Effect of the new derivatives of oxicams on efflux pumps overexpressed in resistant human colorectal adenocarcinoma cell line
2. Synthesis of new piroxicam derivatives and their influence on lipid bilayers
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7. The influence of fluphenazine and its newly synthesized derivatives on the properties of liposomal membranes
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