The aim of this study was to evaluate the immediate and late responses of prostatic cancer in structural and molecular biology in the transgenic adenocarcinoma of the mouse prostate mice (TRAMP), after Goniothalamin and Celecoxib treatments.
The treated mice received Goniothalamin (150mg/Kg, gavage) or Celecoxib (10mg/Kg, gavage) from 8 to 12 weeks of age, which were sacrificed at different ages; the immediate response groups at 12 weeks old and the late response groups at 22 weeks old. The ventral prostate was collected for light microscopy, immunohistochemistry, Western Blotting, TUNEL and ELISA. Morphological analyses indicated that Goniothalamin treatment delayed the prostatic adenocarcinoma progression, 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 experimental periods. Despite Celecoxib diminishing the COX2 and IGFR1 levels, Goniothalamin 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 progression. Celecoxib treatment was efficient in the COX2 regulation in the TRAMP mice, mainly in the advanced disease grade. Finally, we concluded that inflammatory process control in prostate cancer early grades was crucial for the down regulation of the signaling pathways involved in the proliferative processes in advanced cancer grades.
Endocrine-related cancer. 2016 Jan 15 [Epub ahead of print]
Larissa Akemi Kido, Fabio Montico, Rafael Sauce, Aline Barbosa Macedo, Elaine Minatel, Débora Barbosa Vendramini Costa, João Ernesto Carvalho, Ronaldo Aloise Pilli, Valeria Cagnon
L Kido, Department of Structural and Functional Biology, University of Campinas, Campinas, Brazil. , F Montico, Department of Structural and Functional Biology, University of Campinas, Campinas, Brazil. , R Sauce, Department of Structural and Functional Biology, University of Campinas, Campinas, Brazil. , A Macedo, Department of Structural and Functional Biology, University of Campinas, Campinas, Brazil. , E Minatel, Department of Structural and Functional Biology, University of Campinas, Campinas, Brazil. , D Vendramini Costa, Department of Organic Chemistry, University of Campinas , Campinas, Brazil. , J Carvalho, Chemical, Biological and Agricultural Pluridisciplinary Research Center, University of Campinas , Campinas, Brazil. , R Pilli, Department of Organic Chemistry, University of Campinas , Campinas, Brazil. , V Cagnon, Department of Structural and Functional Biology, University of Campinas, Campinas, 13083862, Brazil