The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors
| Autor: | Eleonora Candi, Gaetana Costanza, Mattia Falconi, Alessandro Terrinoni, Laura Diluvio, Luca Bianchi, Elena Campione, Evelin Jasmine Paternò, Augusto Orlandi |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty Skin Neoplasms Tumor suppressor gene Pharmaceutical Science Apoptosis tumor progression Review binding mode medicine.disease_cause Piroxicam Downregulation and upregulation Epidermal growth factor COXs inhibitor actinic keratosis tumor progression binding mode Drug Discovery medicine actinic keratosis Animals Anticarcinogenic Agents Humans Cyclooxygenase Inhibitors COXs inhibitor Pharmacology Settore MED/35 - Malattie Cutanee e Veneree integumentary system business.industry Anti-Inflammatory Agents Non-Steroidal Actinic keratosis lcsh:RM1-950 medicine.disease Molecular Docking Simulation lcsh:Therapeutics. Pharmacology Tumor progression Cancer research Matrix Metalloproteinase 2 Skin cancer Carcinogenesis business medicine.drug |
| Zdroj: | Drug Design, Development and Therapy, Vol 2015, Iss default, Pp 5843-5850 (2015) Drug Design, Development and Therapy |
| Popis: | Elena Campione,1 Evelin Jasmine Paternò,2 Eleonora Candi,3,4 Mattia Falconi,5 Gaetana Costanza,2 Laura Diluvio,1 Alessandro Terrinoni,4 Luca Bianchi,1 Augusto Orlandi2,6,7 1Department of Dermatology, 2Department of Biomedicine and Prevention, 3Department of Experimental Medicine and Surgery, University of Rome “TorVergata”, 4Biochemistry Laboratory IDI-IRCCS, Faculty of Medicine, University of Rome “Tor Vergata”, 5Department of Biology, University of Rome “TorVergata”, 6Institute of Anatomic Pathology, University of Rome “TorVergata”, 7TorVergata University-Policlinic of Rome, Rome, Italy 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 cyclooxygenases-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. Keywords: COXs inhibitor, actinic keratosis, tumor progression, binding mode |
| Databáze: | OpenAIRE |
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