Two dietary polyphenols ameliorate systemic inflammation and wasting associated with HPV16-induced lesions in transgenic mice

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Two dietary polyphenols ameliorate systemic inflammation and wasting associated with HPV16-induced lesions in transgenic mice

Tuesday, 03.01.2017

Authors and Affiliations:

Rui M. Gil da Costa1,2*, Sofia Aragão3, Magda Moutinho3, Antonieta Alvarado3,4, Diogo Carmo5, Fátima Casaca5, Sandra Silva5, Joana Ribeiro2,6, Hugo Sousa2,6, Rita Ferreira7, Rita Nogueira-Ferreira7, Maria João Pires3,8, Bruno Colaço3,8, Rui Medeiros2,6, Carlos Venâncio9, Maria Manuel Oliveira10, Margarida M. S. M. Bastos1, Carlos Lopes11, Paula A. Oliveira3,8

1 LEPABE, Faculty of Engineering - University of Porto (FEUP), Porto, Portugal

2 Molecular Oncology and Viral Pathology Group, CI-IPOP, Porto, Portugal

3 University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal

4 Area de Patologia, Decanato de Ciencias Veterinarias, UCLA, Lara, Venezuela.

5 BMAC - Botelho Moniz Análises Clínicas, Porto, Portugal.

6 Virology Service, IPO-Porto, Porto, Portugal

7 QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal

8 CITAB, UTAD, Quinta de Prados, Vila Real, Portugal.

9 Animal Science Dept., School of Agrarian and Veterinary Sciences, UTAD, Vila Real, Portugal.

10 Centro de Química de Vila Real, UTAD, Vila Real, Portugal.

11 Experimental Pathology and Therapeutics Group, CI-IPOP, Porto, Portugal.

 

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 24 weeks. 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.

 

Journal: Life Sciences

 

Link: http://www.sciencedirect.com/science/article/pii/S0024320516306683