title: Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid.
abstract: Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC in vitro and in vivo. Celecoxib, sulindac, nimesulide, dexamethasone, meclofenamic acid, flufenamic acid and mefenamic acid were tested in UCC HeLa, VIPA, INBL and SiHa cell lines. The cytotoxicity of the drugs was evaluatedin vitro. Celecoxib, sulindac, nimesulide, mefenamic acid and flufenamic acid presented with slight to moderate toxicity (10-40% of cell death corresponding to 100 µM) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (50-90% of cell death corresponding to 100 µM). The meclofenamic acid was tested in murine models (immunodeficient and immunocompetent) of UCC, which manifested a significant reduction in tumor growth and increased mouse survival. It was demonstrated that of the evaluated anti-inflammatory drugs, meclofenamic acid was the most cytotoxic, with a significant antitumor effect in murine models. Subsequent studies are necessary to evaluate the clinical utility of this drug.
authors.affiliation: School of Medicine, University of Colima, Colima, Colima 28030, Mexico ; Cancerology State Institute, Colima State Health Services, Colima, Colima 28000, Mexico.
authors.forename: Alejandro D
authors.initials: AD
authors.lastname: Soriano-Hernandez
authors.affiliation: School of Medicine, University of Colima, Colima, Colima 28030, Mexico.
authors.forename: Daniela
authors.initials: D
authors.lastname: Madrigal-Pérez
authors.affiliation: School of Medicine, University of Colima, Colima, Colima 28030, Mexico ; Cancerology State Institute, Colima State Health Services, Colima, Colima 28000, Mexico.
authors.forename: Hector R
authors.initials: HR
authors.lastname: Galvan-Salazar
authors.affiliation: Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Autononous University of Zacatecas, Zacatecas, Zacatecas 98160, Mexico.
authors.forename: Margarita L
authors.initials: ML
authors.lastname: Martinez-Fierro
authors.affiliation: School of Chemistry, University of Colima, Coquimatlán, Colima 28400, Mexico.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Valdez-Velazquez
authors.affiliation: School of Medicine, University of Colima, Colima, Colima 28030, Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Espinoza-Gómez
authors.affiliation: School of Chemistry, University of Colima, Coquimatlán, Colima 28400, Mexico.
authors.forename: Oscar F
authors.initials: OF
authors.lastname: Vazquez-Vuelvas
authors.affiliation: School of Medicine, University of Colima, Colima, Colima 28030, Mexico.
authors.forename: Bertha A
authors.initials: BA
authors.lastname: Olmedo-Buenrostro
authors.affiliation: General Hospital of Zone No. 1, Mexican Institute of Social Security, Colima, Colima 28000, Mexico.
authors.forename: Jose
authors.initials: J
authors.lastname: Guzman-Esquivel
authors.affiliation: Department of Genetics, School of Medicine, Nuevo Leon Autonomous University, Monterrey, Nuevo León 64460, Mexico.
authors.forename: Iram P
authors.initials: IP
authors.lastname: Rodriguez-Sanchez
authors.affiliation: Cancerology State Institute, Colima State Health Services, Colima, Colima 28000, Mexico.
authors.forename: Agustin
authors.initials: A
authors.lastname: Lara-Esqueda
authors.affiliation: School of Medicine, University of Colima, Colima, Colima 28030, Mexico ; School of Chemistry, University of Colima, Coquimatlán, Colima 28400, Mexico.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Montes-Galindo
authors.affiliation: School of Medicine, University of Colima, Colima, Colima 28030, Mexico ; Cancerology State Institute, Colima State Health Services, Colima, Colima 28000, Mexico.
authors.forename: Ivan
authors.initials: I
authors.lastname: Delgado-Enciso
keywords: antitumor activity; meclofenamic acid; murine model; non-steroidal anti-inflamatory drugs; uterine cervical cancer