Traditional Uyghur medicine Quercus infectoria galls water extract triggers apoptosis and autophagic cell death in colorectal cancer cells

BACKGROUND: The water extract of Quercuse infectoria galls (QIG) is the active ingredient of Uyghur medicine Xipayi Kui Jie’an (KJA) which has promising therapeutic effects on Ulcerative Colitis (UC) as an alternative medicine. Considering the relationship between UC and the development of colorectal cancer (CRC), the present work aims to explore the direct anti-CRC activity of QIG extract. METHODS: CCK8 assay and flow cytometry were used to detect cytotoxicity and apoptosis. Transmission electron microscopy (TEM), flow cytometry, laser confocal and western blotting were performed to examine autophagy. We also adopted Reactive Oxygen Assay kit, as well as transwell and wound healing tests to study the underlying mechanism of QIG against CRC cells. RESULTS: First, we found that QIG extract could suppress the viability of CRC cells and trigger caspases-dependent apoptosis. Subsequently, we proved for the first time that QIG extract also triggered autophagic cell death in CRC cells, which together with apoptosis contributed to the cytotoxic effect on CRC cells. Further investigation revealed that QIG-induced cytotoxicity associated with intracellular ROS accumulation which could suppress the AKT/mTOR signaling pathway, and then induce autophagy and inhibit cell growth. Besides, Erk signaling pathway was also involved in the process of autophagic cell death. Moreover, QIG extract also influenced EMT process and inhibited CRC cell migration. CONCLUSION: Altogether, this study provides a basis for the utilization of QIG as an alternative medicine for CRC prevention and treatment.