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Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth
- 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.
- Subjects :
- Male
Vascular Endothelial Growth Factor A
0301 basic medicine
Time Factors
Angiogenesis
Angiogenesis Inhibitors
Apoptosis
B7-H1 Antigen
VEGF-A
0302 clinical medicine
Cell Movement
Antineoplastic Combined Chemotherapy Protocols
Nutrition and Dietetics
Neovascularization, Pathologic
Settore BIO/14
Tumor Burden
bladder cancer
ellagic acid
polyphenolic compounds
urothelial cancer
030220 oncology & carcinogenesis
lcsh:Nutrition. Foods and food supply
Signal Transduction
Mitomycin
Mice, Nude
lcsh:TX341-641
Biology
Article
Inhibitory Concentration 50
03 medical and health sciences
Ellagic Acid
In vivo
Cell Line, Tumor
medicine
Animals
Humans
Neoplasm Invasiveness
Cell Proliferation
Bladder cancer
Dose-Response Relationship, Drug
Mitomycin C
Cancer
Chemotaxis
medicine.disease
Vascular Endothelial Growth Factor Receptor-2
Xenograft Model Antitumor Assays
Immune checkpoint
In vitro
030104 developmental biology
Urinary Bladder Neoplasms
Immunology
Cancer research
Food Science
Subjects
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