title: Anti-inflammatory therapies in TRAMP mice: delay in PCa progression.
abstract: The aim of this study was to characterize the structural and molecular biology as well as evaluate the immediate and late responses of prostatic cancer in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model after treatment with goniothalamin (GTN) and celecoxib. The treated mice received GTN (150 mg/kg, gavage) or celecoxib (10 mg/kg, gavage) from 8 to 12 weeks of age. They were killed at different ages: the immediate-response groups at 12 weeks and the late-response groups at 22 weeks. The ventral prostate was collected for light microscopy, immunohistochemistry, western blotting, TUNEL, and ELISA. Morphological analyses indicated that GTN treatment delayed the progression of prostatic adenocarcinoma, leading to a significant decrease of prostatic lesion frequency in both experimental period responses to this treatment, mainly high-grade prostatic intraepithelial neoplasia and well-differentiated adenocarcinoma. Also, the celecoxib treatment showed a particular decrease in the proliferative processes (PCNA) in both the experimental periods. Despite celecoxib diminishing the COX2 and IGFR1 levels, GTN presented higher action spectrum considering the decrease of a greater molecular number involved in the proliferative and inflammatory processes in prostatic cancer. Goniothalamin attenuated the pro-inflammatory response in TRAMP prostatic microenvironment, delaying prostate cancer (PCa) progression. Celecoxib treatment was efficient in the regulation of COX2 in the TRAMP mice, mainly in the advanced disease grade. Finally, we concluded that inflammatory process control in early grades of PCa was crucial for the downregulation of the signaling pathways involved in the proliferative processes in advanced cancer grades.
authors.affiliation: Department of Structural and Functional BiologyStructural and Cellular Biology Postgraduate Program, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Larissa Akemi
authors.initials: LA
authors.lastname: Kido
authors.affiliation: Department of Structural and Functional BiologyStructural and Cellular Biology Postgraduate Program, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Fabio
authors.initials: F
authors.lastname: Montico
authors.affiliation: Department of Structural and Functional BiologyStructural and Cellular Biology Postgraduate Program, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Sauce
authors.affiliation: Department of Structural and Functional BiologyStructural and Cellular Biology Postgraduate Program, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Aline Barbosa
authors.initials: AB
authors.lastname: Macedo
authors.affiliation: Department of Structural and Functional BiologyStructural and Cellular Biology Postgraduate Program, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Elaine
authors.initials: E
authors.lastname: Minatel
authors.affiliation: Chemical, Biological and Agricultural Pluridisciplinary Research CenterCPQBA, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil Department of Organic ChemistryInstitute of Chemistry, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Débora Barbosa Vendramini
authors.initials: DB
authors.lastname: Costa
authors.affiliation: Chemical, Biological and Agricultural Pluridisciplinary Research CenterCPQBA, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil Faculty of Pharmaceutical SciencesUniversity of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: João Ernesto de
authors.initials: JE
authors.lastname: Carvalho
authors.affiliation: Department of Organic ChemistryInstitute of Chemistry, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Ronaldo Aloise
authors.initials: RA
authors.lastname: Pilli
authors.affiliation: Department of Structural and Functional BiologyStructural and Cellular Biology Postgraduate Program, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil quitete@unicamp.br.
authors.forename: Valeria Helena Alves
authors.initials: VH
authors.lastname: Cagnon
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D000068579:Celecoxib / Q000494:pharmacology / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011753:Pyrones / Q000494:pharmacology / Q000627:therapeutic use; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D053583:Interleukin-1beta; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D011753:Pyrones; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C103280:goniothalamin; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D017526:Receptor, IGF Type 1; D000068579:Celecoxib
keywords: TRAMP; anti-inflammatory therapies; goniothalamin; inflammation; prostate cancer