title: The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors.
abstract: 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.
authors.affiliation: Department of Dermatology, University of Rome "Tor Vergata" Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Campione
authors.affiliation: Department of Biomedicine and Prevention, University of Rome "Tor Vergata" Rome, Italy.
authors.forename: Evelin Jasmine
authors.initials: EJ
authors.lastname: Paternò
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata" Rome, Italy ; Biochemistry Laboratory IDI-IRCCS, Faculty of Medicine, University of Rome "Tor Vergata" Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Candi
authors.affiliation: Department of Biology, University of Rome "Tor Vergata" Rome, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Falconi
authors.affiliation: Department of Biomedicine and Prevention, University of Rome "Tor Vergata" Rome, Italy.
authors.forename: Gaetana
authors.initials: G
authors.lastname: Costanza
authors.affiliation: Department of Dermatology, University of Rome "Tor Vergata" Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Diluvio
authors.affiliation: Biochemistry Laboratory IDI-IRCCS, Faculty of Medicine, University of Rome "Tor Vergata" Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Terrinoni
authors.affiliation: Department of Dermatology, University of Rome "Tor Vergata" Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Bianchi
authors.affiliation: Department of Biomedicine and Prevention, University of Rome "Tor Vergata" Rome, Italy ; Institute of Anatomic Pathology, University of Rome "Tor Vergata" Rome, Italy ; Tor Vergata University-Policlinic of Rome, Rome, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D062105:Molecular Docking Simulation; D010894:Piroxicam / Q000494:pharmacology / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D016861:Cyclooxygenase Inhibitors; D010894:Piroxicam; D020778:Matrix Metalloproteinase 2
keywords: COXs inhibitor; actinic keratosis; binding mode; tumor progression