The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors

• Published in: Drug design, development and therapy development and therapy, 2015-01, Vol.9 (default), p.5843-5850
• Main Authors: Campione, Elena, Paternò, Evelin Jasmine, Candi, Eleonora, Falconi, Mattia, Costanza, Gaetana, Diluvio, Laura, Terrinoni, Alessandro, Bianchi, Luca, Orlandi, Augusto
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Anticarcinogenic Agents - pharmacology; Anticarcinogenic Agents - therapeutic use; Apoptosis; Apoptosis - drug effects; Cancer; Carcinogenesis; Carcinogens; Chemotherapy; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase Inhibitors - therapeutic use; Cyclooxygenase-1; Cyclooxygenase-2; Deregulation; Dosage and administration; Drug targeting; Drug therapy; Epidermal growth factor; Growth factors; Humans; Inflammation; Innovations; Invasiveness; Matrix Metalloproteinase 2 - metabolism; Metalloproteinase; Molecular docking; Molecular Docking Simulation; Mutation; Nonsteroidal anti-inflammatory drugs; Ornithine; Ornithine decarboxylase; Pathogenesis; Piroxicam; Piroxicam - pharmacology; Piroxicam - therapeutic use; Polyamines; Prevention; Prostaglandins; Review; Skin cancer; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Skin Neoplasms - prevention & control; Tumor suppressor genes; Tumors; Vascular endothelial growth factor
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S84849

Piroxicam (PXM), a nonsteroidal anti-inflammatory drug, is an enolic benzothiazine and a potent member of the oxicam series. The drug suppresses the synthesis of proinflammatory enzymes, such as cyclo-oxygenases-1 and -2 (COX-1 and 2), downregulates the production of prostaglandins (PGs) and tromboxanes, and inhibits polyamines production by blocking ornithine decarboxylase induction involved in nonmelanoma skin carcinogenesis. In addition, PXM is able to induce tumor cell apoptosis and suppresses metalloproteinase 2 activities. Skin carcinogenesis is a multistep process in which the accumulation of genetic events leads to a gradually dysplastic cellular expression, deregulation of cell growth, and carcinomatous progression. COX-1 upregulation plays a significant role in PG and vascular epidermal growth factor production supporting tumor growth. Increased level of PGs in premalignant and/or malignant cutaneous tumors is also favored by upregulation of COX-2 and downregulation of the tumor suppressor gene 15-hydroxy-prostaglandin dehydrogenase. Chemoprevention can be a hopeful approach to inhibit carcinoma occurrence before an invasive tumor develops. The chemopreventive effect of nonsteroidal anti-inflammatory drugs on nonmelanoma skin cancers has been established. In this study, we highlighted the different modalities of action of PXM on the pathogenesis of nonmelanoma skin cancer, analyzing and evaluating binding modes and energies between COX-1 or COX-2 and PXM by protein-ligand molecular docking. Our clinical experience about the local use of PXM on actinic keratoses and field cancerization is also reported, confirming its efficacy as target therapy.