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Short and Long‐term Pro‐Inflammatory Mediator Responses in Prostate Adenocarcinoma Progression in TRAMP Mice after Goniothalamin Therapy
Author(s) -
Cag Valeria,
Kido Larissa,
Montico Fabio,
Costa Debora,
Carvalho Joao,
Pilli Ronaldo
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.558.1
Subject(s) - tramp , prostate , stat3 , prostate cancer , inflammation , medicine , adenocarcinoma , lesion , mediator , endocrinology , tumor necrosis factor alpha , pathology , cancer , chemistry , apoptosis , biochemistry
The role of pro‐inflammatory mediators has been widely investigated due to their relevance in prostate cancer (CaP). The aim of the study was to evaluate the short and long term responses of pro‐inflammatory mediators correlated with different grades of CaP in TRAMP mice after Goniothalamin treatment. The control groups were TC8, TC12 and TC22 (8, 12 and 22 week‐old mice). The treated groups received Goniothalamin (150mg/Kg, orally) for 4 weeks (from 8 to 12 week‐old mice) and were sacrificed at different ages, (T1GTN group/12 week‐old mice and T2GTN group/22 week‐old mice). The ventral lobe was collected for light microscopy, ELISA and Western Blotting analyses. Low‐grade and high‐grade PIN in TC8 and TC12 groups were observed. Well‐developed and undifferentiated adenocarcinoma characterized the prostate in the TC22 group. The Goniothalamin treatment led to a decrease of lesion frequency in the treated groups. Decreased NF‐κB and p‐STAT3 levels were seen in TRAMP mice immediately after the treatment. Despite having higher levels of these molecules in the T2GTN group, these levels still showed a decrease in relation to the TC22 group. TNF‐α, IL‐17 and IL1‐β serum levels showed a tendency to decrease with the treatment. The Goniothalamin reduced pro‐tumorigenic effects related to inflammation in the prostate in early and late neoplastic development. Also, the reduction of NF‐kB and p‐STAT3 transcription factor levels led to decreased proliferative process frequency. Thus, the Goniothalamin significantly lessened the pro‐inflammatory signaling, retarding lesion progression and highlighting the relevance of the inflammatory process in early CaP development. Fapesp 2013/01294‐8, 23049‐5