Abstract
BackgroundThe 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.MethodsCCK8 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.ResultsFirst, 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.ConclusionAltogether, this study provides a basis for the utilization of QIG as an alternative medicine for CRC prevention and treatment.
Highlights
Global cancer statistics data show the prevalence of colorectal cancer (CRC) ranks third in the world in 2018, with approximately 1,800,000 people being diagnosed with CRC each year [1]
Cytotoxicity induced by Quercuse infectoria galls (QIG) on CRC cells The growth and morphology of the CRC cells were photographed under an inverted microscope
The cytotoxicity of QIG was assessed by the CCK8 kit, and the data indicated that QIG suppressed the viability of CRC cells in a time and dose-dependent fashion (Fig. 1c and d)
Summary
Global cancer statistics data show the prevalence of colorectal cancer (CRC) ranks third in the world in 2018, with approximately 1,800,000 people being diagnosed with CRC each year [1]. QIG is rich in tannins with about 50–70%, followed by gallic acid, ellagic acid, hexamethyl, syringic acid, amentoflavone, sitosterol and glucose propionic acid [7, 8] It has various pharmacological activities including antifungal, antiviral, insecticidal, astringent, wound healing, gastric protective effects and antiulcer, and the most important use of it is to treat UC [9]. Considering the therapeutic effects of KJA on UC and the relationship between UC and CRC, we wonder whether the water extract of QIG has direct anti-tumor activity to CRC cells. 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
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