Brazilian Berry Extract, High‐Fat Diet and Prostate Cancer: In Vitro and In Vivo Evaluation of Inflammation and Extracellular Matrix

Abstract

The high incidence of prostatic cancer (PCa) has encouraged studies in prostatic cellular biology all over the world. In addition, Brazilian berries, such as Myrciaria jaboticaba (Vell.) Berg, show a high polyphenol concentration in the peel, characterizing antioxidative and anti‐inflammatory properties. The aim herein was to analyze the anti‐inflammatory and remodeling tissue effects of the Jaboticaba peel extract (JPE), a patented product, in early prostatic adenocarcinoma development associated with high‐fat diet (HFD) intake, as well as to investigate the JPE role in human PCa and LNCaP cell lines. TRAMP mice from control groups received standard diet or HFD and the treated groups followed the same diet protocol plus JPE (5.8g/Kg/body weight during 5 days per week for 2 months). The dorsolateral prostate was collected for immunohistochemistry and Western Blotting analyses. PC‐3 and LNCaP cells were treated with different doses of JPE (125, 250, 500 ug/mL) and used for cellular viability assay and Western Blotting analyses. The results showed that the HFD intake led to an MMP‐9 increase and a Laminin protein level decrease, worsening the PCa profile in this transgenic model. Conversely, JPE led to decreased MMP‐9 and also TGF‐beta after HFD intake. Laminin level increased in both groups treated with JPE. Dose and time dependent JPE exposure reduced cellular viability, especially, in androgen‐responsive LNCaP cells. In addition, JPE induced NfkB and iNOS reduction not only in LNCaP but also in PC‐3 cell lines, suggesting that the growth inhibitory effect of JPE in PCa may be associated with its anti‐inflammatory role. To conclude, the tissue damage caused by HFD led to the deregulation of the extracellular matrix elements, which intensified cancer progression, compromising the epithelial‐stromal interaction in the dorsolateral prostate. However, JPE was beneficial for the dynamic interaction between the epithelium and stroma in vivo, and altered cancer cell growth by means of anti‐inflammatory pathway, pointing towards a possible adjuvant therapy for PCa delay, highlighting the natural compounds as an important strategy in prostatic disorders.Support or Funding InformationSao Paulo Research Foundation/FAPESP (2018 04579‐7). And Fund for Support to Teaching, Research and Outreach Activities FAEPEX/UNICAMP (2080/20)