Prevention of Prostate Cancer in Transgenic Adenocarcinoma of the Mouse Prostate Mice by Yellow Passion Fruit Extract and Antiproliferative Effects of Its Bioactive Compound Piceatannol

Author(s)

Kido, Larissa Akemi ^{[1, 2]} ; Hahm, Eun-Ryeong ^[3] ; Kim, Su-Hyeong ^[3] ; Baseggio, Andressa Mara ^[2] ; Cagnon, Valeria Helena Alves ^[1] ; Singh, Shivendra V. ^{[3, 4]} ; Marostica, Jr., Mario Roberto ^[2]

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas - Brazil

^[2] Univ Estadual Campinas, Fac Food Engn, Dept Food & Nutr, Campinas - Brazil

^[3] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 - USA

^[4] Univ Pittsburgh, Sch Med, UPMC Hillman Canc Ctr, Pittsburgh, PA 15260 - USA

• Document type: Journal article
• Source: JOURNAL OF CANCER PREVENTION; v. 25, n. 2, p. 87-99, JUN 2020.
• Web of Science Citations: 3

Abstract

Piceatannol (PIC), a polyphenol presents in many vegetables and fruits including yellow passion fruit extract (PFE; Passiflora edulis), has anti-cancer activity, but its molecular targets are still poorly understood. The aims of this study were to investigate the molecular mechanistic actions of PIC in prostate cancer cell lines and to test if the extract from PFE rich in PIC can affect the growth of prostate cancer cells in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. The PC-3, 22Rv1, LNCaP, and VCaP prostate cancer cells were exposed to PIC (10-40 mu M) and cell viability, lactate measurement, Western blot, and flow cytometric analyses were performed. For an in vivo experiments, eight-week-old TRAMP mice (n = 10 per group each) received an aqueous extract of PFE containing 20 mg of PIC/kg or water (control group) by gavage for 4 or 10 weeks for further analyses. PIC treatment concentration- and time-dependently reduced viability of all cell lines tested. 22Rv1 and LNCaP cells treated with PIC did not exhibit any significant alteration in the intracellular accumulation of lactate. PIC treatment caused G(0)/G(1) phase cell cycle arrest and induction of apoptosis in both LNCaP and 22Rv1 cells. PIC-treated cells exhibited altered protein levels of p53, p21, cyclin D1, and cyclin-dependent kinase 4 (cdk4). The short and long-term PFE treatments also affected p21, cyclin D1 and cdk4 and delayed disease progression in TRAMP, with a decreased incidence of preneoplastic lesions. In conclusion, PIC apparently does not alter glucose metabolism in prostate cancer cells, while cell cycle arrest and p53 modulation are likely important in anti-cancer effects of PIC alone or as a food matrix byproduct in prostate cancer cells, especially those with an androgen-dependent phenotype. (AU)

• FAPESP's process: 18/11069-5 - Action of Brazilian berries on metabolic parameters and cognitive performance of obese animals
• Grantee: Mário Roberto Maróstica Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/13320-9 - Effect of pulp oil and tea of leaves from avocado Hass variety associated with physical activity in the treatment of obesity induced by high-fat diet
• Grantee: Mário Roberto Maróstica Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/50333-1 - COBRA: a novel compound discovery pipeline for rapid and cost-effective identification of bioactives with health beneficial effects in Brazilian crops
• Grantee: Glaucia Maria Pastore
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 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
• Grantee: Larissa Akemi Kido de Barros
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor