Introduction: Esophageal squamous cell carcinoma (ESCC) is a prevalent and lethal cancer, with traditional treatments often ineffective. This study investigates the anti-proliferative and anti-metastatic effects of natural compounds Urolithin A (UA) and Urolithin B (UB) on ESCC cell lines KYSE-30 and YM-1.
Methods: KYSE-30 and YM-1 ESCC cells were treated with UA and UB, and their viability assays, cell cycle arrest, apoptosis, expressions of mRNA linked to apoptosis and metastasis, generation of reactive oxygen species (ROS), activity of MMP-2 and MMP-9, along with mRNA expressions of MMP-2 and MMP-9, and migration were assessed.
Results: The results showed that UA (which had lower IC50 than UB) and UB reduced the viability of both KYSE-30 and YM-1 cells. Furthermore, UA and UB exhibited lower toxicity towards normal HFF cells compared to ESCC cells. Both UB and the more effective UA induced apoptosis and caused G2/M cell cycle arrest in KYSE-30 and YM-1 cells. Additionally, UA and UB elevated ROS production and led to a decrease in Bcl-2 expression while increasing the expression of Bax and p21 genes. A decrease in the mRNA expression and enzymatic activity of MMP-2 and MMP-9 was observed following treatment with UA and UB.
Conclusion: UB and, more potently, UA show the potential to induce apoptosis while reducing metastatic properties and migration of ESCC cells, suggesting them as promising candidates for new anti-ESCC therapies; however, further preclinical and clinical research is needed to fully understand their anti-cancer effects and mechanisms.
Keywords: Apoptosis; Esophageal cancer; Esophageal squamous cell carcinoma; Matrix metalloproteinase; Migration; Urolithin A; Urolithin B.
© 2025. The Author(s), under exclusive licence to Tehran University of Medical Sciences.