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Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth

Authors :
Elena Bonanno
Giuseppe Vespasiani
Maria Grazia Atzori
Roberto Miano
Claudia Ceci
Pedro Miguel Lacal
Maurizio Mattei
Grazia Graziani
Lucio Tentori
Manuel Scimeca
Maria Gabriella De Martino
Rosella Cicconi
Source :
Nutrients; Volume 8; Issue 11; Pages: 744, Nutrients, Nutrients, Vol 8, Iss 11, p 744 (2016)
Publication Year :
2016
Publisher :
Multidisciplinary Digital Publishing Institute, 2016.

Abstract

Ellagic acid (EA) is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA influence on bladder cancer cell invasion of the extracellular matrix triggered by vascular endothelial growth factor-A (VEGF-A), an angiogenic factor associated with disease progression and recurrence, and tumor growth in vivo. In this study, we have investigated EA activity against four different human bladder cancer cell lines (i.e., T24, UM-UC-3, 5637 and HT-1376) by in vitro proliferation tests (measuring metabolic and foci forming activity), invasion and chemotactic assays in response to VEGF-A and in vivo preclinical models in nude mice. Results indicate that EA exerts anti-proliferative effects as a single agent and enhances the antitumor activity of mitomycin C, which is commonly used for the treatment of bladder cancer. EA also inhibits tumor invasion and chemotaxis, specifically induced by VEGF-A, and reduces VEGFR-2 expression. Moreover, EA down-regulates the expression of programmed cell death ligand 1 (PD-L1), an immune checkpoint involved in immune escape. EA in vitro activity was confirmed by the results of in vivo studies showing a significant reduction of the growth rate, infiltrative behavior and tumor-associated angiogenesis of human bladder cancer xenografts. In conclusion, these results suggest that EA may have a potential role as an adjunct therapy for bladder cancer.

Details

Language :
English
ISSN :
20726643
Database :
OpenAIRE
Journal :
Nutrients; Volume 8; Issue 11; Pages: 744
Accession number :
edsair.doi.dedup.....7f679a96130fcf54e6ff607e96d928cb
Full Text :
https://doi.org/10.3390/nu8110744