title: HPV16 induces a wasting syndrome in transgenic mice: Amelioration by dietary polyphenols via NF-κB inhibition.
abstract: Cancer patients often show a wasting syndrome for which there are little therapeutic options. Dietary polyphenols have been proposed for treating this syndrome, but their usefulness in cases associated with human papillomavirus (HPV)-induced cancers is unknown. We characterized HPV16-transgenic mice as a model of cancer cachexia and tested the efficacy of long-term oral supplementation with polyphenols curcumin and rutin. Both compounds were orally administered to six weeks-old HPV16-transgenic mice showing characteristic multi-step skin carcinogenesis, for 24weeks. Skin lesions and blood, liver and spleen inflammatory changes were characterized histologically and hematologically. Hepatic oxidative stress, skeletal muscle mass and the levels of muscle pro-inflammatory transcription factor NF-κB were also assessed. Skin carcinogenesis was associated with progressive, severe, systemic inflammation (leukocytosis, hepatitis, splenitis), significant mortality and cachexia. Curcumin and rutin totally suppressed mortality while reducing white blood cells and the incidence of splenitis and hepatitis. Rutin prevented muscle wasting more effectively than curcumin. Preservation of muscle mass and reduced hepatic inflammation were associated with down-regulation of the NF-κB canonical pathway and with reduced oxidative stress, respectively. These results point out HPV16-transgenic mice as a useful model for studying the wasting syndrome associated with HPV-induced cancers. Dietary NF-κB inhibitors may be useful resources for treating this syndrome.
authors.affiliation: LEPABE, Faculty of Engineering-University of Porto (FEUP), Porto, Portugal; Molecular Oncology and Viral Pathology Group, CI-IPOP, Porto, Portugal. Electronic address: rmcosta@fe.up.pt.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Gil da Costa
authors.affiliation: University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: Aragão
authors.affiliation: University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
authors.forename: Magda
authors.initials: M
authors.lastname: Moutinho
authors.affiliation: University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Area de Patologia, Decanato de Ciencias Veterinarias, UCLA, Lara, Venezuela.
authors.forename: Antonieta
authors.initials: A
authors.lastname: Alvarado
authors.affiliation: BMAC-Botelho Moniz Análises Clínicas, Porto, Portugal.
authors.forename: Diogo
authors.initials: D
authors.lastname: Carmo
authors.affiliation: BMAC-Botelho Moniz Análises Clínicas, Porto, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Casaca
authors.affiliation: BMAC-Botelho Moniz Análises Clínicas, Porto, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Silva
authors.affiliation: Molecular Oncology and Viral Pathology Group, CI-IPOP, Porto, Portugal; Virology Service, IPO-Porto, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Ribeiro
authors.affiliation: Molecular Oncology and Viral Pathology Group, CI-IPOP, Porto, Portugal; Virology Service, IPO-Porto, Porto, Portugal.
authors.forename: Hugo
authors.initials: H
authors.lastname: Sousa
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Nogueira-Ferreira
authors.affiliation: University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; CITAB, UTAD, Quinta de Prados, Vila Real, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Pires
authors.affiliation: University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; CITAB, UTAD, Quinta de Prados, Vila Real, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Colaço
authors.affiliation: Molecular Oncology and Viral Pathology Group, CI-IPOP, Porto, Portugal; Virology Service, IPO-Porto, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
authors.affiliation: Animal Science Dept., School of Agrarian and Veterinary Sciences, UTAD, Vila Real, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Venâncio
authors.affiliation: Centro de Química de Vila Real, UTAD, Vila Real, Portugal.
authors.forename: Maria Manuel
authors.initials: MM
authors.lastname: Oliveira
authors.affiliation: LEPABE, Faculty of Engineering-University of Porto (FEUP), Porto, Portugal.
authors.forename: Margarida M S M
authors.initials: MM
authors.lastname: Bastos
authors.affiliation: Experimental Pathology and Therapeutics Group, CI-IPOP, Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.affiliation: University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; CITAB, UTAD, Quinta de Prados, Vila Real, Portugal.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002100:Cachexia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D003474:Curcumin / Q000627:therapeutic use*; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology / Q000821:virology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D012431:Rutin / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000821:virology; D012878:Skin Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D019282:Wasting Syndrome / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000821:virology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D012431:Rutin; D003474:Curcumin
keywords: Cachexia; Cancer; Curcumin; HPV; NF-κB; Rutin