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Effects of passion fruit bagasse extract (Passiflora edulis) in vitro and in vivo: chemopreventive and anti-inflammatory role of phenolic compounds in prostate cancer progression

Grant number: 17/01573-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2017
Effective date (End): December 31, 2020
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal Investigator:Mário Roberto Maróstica Junior
Grantee:Larissa Akemi Kido de Barros
Home Institution: Faculdade de Engenharia de Alimentos (FEA). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):18/09793-7 - A comparative study based on the piceatannol isolated and as part of the bioactive content of the passion fruit bagasse extract (PFBE) in prostate cancer therapy, BE.EP.PD

Abstract

Prostate cancer is an aging associated disease and one of the greatest public health problems in all the world. Inflammation plays an important role in the onset and prostatic lesions progression, and is often related to the aging process. In this sense, cancer prevention methods by means of natural sources emerged as a strategy in disease control, and discovery of new substances and methodologies for therapeutic interventions. Thus, the aim of this study will be to characterize the passion fruit bagasse extract in relation to its bioactive compounds content, antioxidant, antiproliferative, anti-inflammatory and chemopreventive properties, considering chemical and biological aspects associated with prostate cancer in vitro and in vivo. For such purpose, the defatted passion fruit bagasse extraction will be carried out by means pressurized liquid extraction to obtain piceatannol and scirpusin B, and the chemical characterization will be performed by total and specific phenolic compounds analysis, and evaluation of the antioxidant capacity in vitro by ORAC and FRAP assays. Prostate tumor cells (TRAMP-C1) will be used in order to determine the influence of passion fruit bagasse extract treatment by gene expression evaluation of NfºB pathway targets, as well as protein quantification of NfºB p65, IkB±, IkB², COX-2, iNOS, TNF-±, STAT-3, BCL-2, BCL-xL, BAX. Also, immunoenzymatic assays will be performed to verify production and secretion levels of inflammatory inducing factors, such as IL-1², IL-6 and TNF-±, as well as caspases 3, 9 and 8 activity. In vivo experiments will be executed in transgenic adenocarcinoma of mouse prostate (TRAMP), which will be divided into 3 control groups: 8 (T8), 12 (T12) and 18 (T18) weeks of age. The T12 group will receive water by gavage for 4 weeks from the eighth week of life, while the T18 group will receive the same treatment for 10 weeks. The groups treated with the passion fruit bagasse extract will be divided into: TRAMP/Passion fruit bagasse extract group (TEM): TRAMP 8 weeks old will receive 20 mg/kg of piceatannol contained in the extract for 4 weeks; and TRAMP chronic treatment group (TEMC): TRAMP with 8 weeks old, will receive the same treatment as the TEM group for 10 weeks. The prostatic ventral lobe will be collected for morphological classification of prostatic lesions. The passion fruit bagasse extract chemopreventive potential will be evaluated by gene expression and protein levels quantification following the same parameters performed in the in vitro assays. Furthermore, cell proliferation and apoptosis indices will be determined by PCNA immunostaining and TUNEL, respectively. (AU)