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-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.