期刊
MOLECULAR CARCINOGENESIS
卷 57, 期 2, 页码 193-200出版社
WILEY
DOI: 10.1002/mc.22746
关键词
autophagy; colorectal cancer; matrix metallo proteinases; metastasis; urolithin A
资金
- National Science Foundation of China [21201124]
- Beijing Municipal Institutions [CITTCD201304176]
- Chinese Government [Z141100002114049, KM201310025007]
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.
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