Metabolite of ellagitannins, urolithin A induces autophagy and inhibits metastasis in human sw620 colorectal cancer cells

Autophagy is an evolutionarily conserved pathway in which cytoplasmic contents are degraded and recycled. This study found that submicromolar concentrations of urolithin A, a major polyphenol metabolite, induced autophagy in SW620 colorectal cancer (CRC) cells. Exposure to urolithin A also dose‐depe...

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Bibliographic Details
Published in:Molecular carcinogenesis 2018-02, Vol.57 (2), p.193-200
Main Authors: Zhao, Wenhua, Shi, Fengqiang, Guo, Zhikun, Zhao, Jiaojie, Song, Xueying, Yang, Hua
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis - drug effects
Autophagy
Autophagy - drug effects
Caspases - metabolism
Cell cycle
Cell death
Cell Line, Tumor
Cell migration
Cell Movement - drug effects
Cell proliferation
Cell Proliferation - drug effects
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - metabolism
Coumarins - pharmacology
DNA biosynthesis
Gelatinase B
Humans
Hydrolyzable Tannins - pharmacology
matrix metallo proteinases
Matrix Metalloproteinase 9 - metabolism
Metastases
Metastasis
Phagocytosis
RNA, Small Interfering - metabolism
siRNA
urolithin A
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Summary:Autophagy is an evolutionarily conserved pathway in which cytoplasmic contents are degraded and recycled. This study found that submicromolar concentrations of urolithin A, a major polyphenol metabolite, induced autophagy in SW620 colorectal cancer (CRC) cells. Exposure to urolithin A also dose‐dependently decreased cell proliferation, delayed cell migration, and decreased matrix metalloproteinas‐9 (MMP‐9) activity. In addition, inhibition of autophagy by Atg5‐siRNA, caspases by Z‐VAD‐FMK suppressed urolithin A‐stimulated cell death and anti‐metastatic effects. Micromolar urolithin A concentrations induced both autophagy and apoptosis. Urolithin A suppressed cell cycle progression and inhibited DNA synthesis. These results suggest that dietary consumption of urolithin A could induce autophagy and inhibit human CRC cell metastasis. Urolithins may thus contribute to CRC treatment and offer an alternative or adjunct chemotherapeutic agent to combat this disease.
ISSN:0899-1987
1098-2744
DOI:10.1002/mc.22746