Study on the Effect of Total Coumarins from Pileostegia tomen-tella Inducing Ferroptosis of Colorectal Cancer Cells
Total Coumarins from Pileostegia tomentella(TCPT)was a traditional Yao medicine in Guangxi,to explore the effect and mechanism of TCPT in inducing ferroptosis of colorectal cancer HT-29 cells,human Colorectal Cancer(CRC)HT-29 cells were treated with different concentrations of TCPT in this study,and the changes of cell viability were detected by Cell Counting Kit-8(CCK-8)combined with Flow Cytometry(FCM).The morphological changes of mitochondria were observed by transmission electron microscopy,and the changes of intracellular iron-dependent Reactive Oxygen Species(ROS)content were detected by di-chlorofluorescein(DCFH-DA)dye probe method.The specific fluorescent probe BODIPY 581/589 C11 was used to detect intracellular lipid peroxide content.The expression levels of ferroptosis-related proteins Gluta-thione Peroxidase 4(GPX4),Nuclear receptor Coactivator 4(NCOA4),Cysteine-glutamate antiporter sub-unit(xCT)and Divalent Metal Transporter 1(DMT1)proteins in HT-29 cells were detected by Western blotting.The results showed that after TCPT treatment,the cell viability of human colorectal cancer HT-29 cells decreased in a concentration-dependent manner.Cell mitochondria showed typical ferroptosis morpho-logical characteristics such as cytoplasmic sudden reduction,ridge collapse,and'concentric circles'.The levels of intracellular ROS and lipid peroxides in the cells were significantly increased in a dose-dependent manner.The expression levels of ferroptosis marker proteins GPX4 and xCT in HT-29 cells were down-reg-ulated,while the expression levels of NCOA4 and DMT1 were up-regulated.In summary,the total couma-rin from Pileostegia tomentella can significantly increase the levels of intracellular ROS and lipid peroxida-tion,thus inducing ferroptosis in colorectal cancer HT-29 cells,which may be one of its anti-colorectal canc-er mechanisms.
Yao medicinePileostegia tomentellatotal coumarinsferroptosisColorectal Cancer(CRC)
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