Objective:To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells.Methods:Breast cancer 4T1 cells were divided into 6 groups:control,brazilin 1/2 half maximal inhibitory concentrati...Objective:To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells.Methods:Breast cancer 4T1 cells were divided into 6 groups:control,brazilin 1/2 half maximal inhibitory concentration(IC_(50)),IC_(50),2×IC_(50),erastin(10μg/mL)and capecitabine(10μg/mL)groups.The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay,and the treatment dose of brazilin was screened.The effect of brazilin on the mitochondrial morphology of 4T1 cells,and the mitochondrial damage was evaluated under electron microscopy.The levels of Fe+,reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH)and glutathione peroxidase 4(GPX4)were estimated using various detection kits.The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay.The expressions levels of tumor protein p53,solute carrier family 7 member 11(SLC7A11),GPX4 and acyl-CoA synthetase long-chain family member 4(ACSL4)proteins were quantified by Western blot assay.Results:Compared to the control group,the 10(1/2 IC_(50)),20(IC_(50))and 40(2×IC_(50))μg/mL brazilin,erastin,and capecitabine groups showed a significant decrease in the cell survival rate,invasion and migration abilities,GSH,SLC7A11 and GPX4 protein expression levels,and mitochondrial volume and ridge(P<0.05),and a significant increase in the mitochondria membrane density,Fe2+,ROS and MDA levels,and p53 and ACSL4 protein expression levels(P<0.05).Conclusions:Brazilin actuated ferroptosis in breast cancer cells,and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.展开更多
基金Supported by National Administration of Traditional Chinese Medicine Youth Qihuang Scholars Talent Project,the 73rd Batch of Grant from China Postdoctoral Science Foundation(No.2023M731069)Traditional Chinese Medicine Administration Project of Hunan Province(No.B2023086)Health Research Project of Hunan Provincial Health Commission(No.W20243081)。
文摘Objective:To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells.Methods:Breast cancer 4T1 cells were divided into 6 groups:control,brazilin 1/2 half maximal inhibitory concentration(IC_(50)),IC_(50),2×IC_(50),erastin(10μg/mL)and capecitabine(10μg/mL)groups.The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay,and the treatment dose of brazilin was screened.The effect of brazilin on the mitochondrial morphology of 4T1 cells,and the mitochondrial damage was evaluated under electron microscopy.The levels of Fe+,reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH)and glutathione peroxidase 4(GPX4)were estimated using various detection kits.The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay.The expressions levels of tumor protein p53,solute carrier family 7 member 11(SLC7A11),GPX4 and acyl-CoA synthetase long-chain family member 4(ACSL4)proteins were quantified by Western blot assay.Results:Compared to the control group,the 10(1/2 IC_(50)),20(IC_(50))and 40(2×IC_(50))μg/mL brazilin,erastin,and capecitabine groups showed a significant decrease in the cell survival rate,invasion and migration abilities,GSH,SLC7A11 and GPX4 protein expression levels,and mitochondrial volume and ridge(P<0.05),and a significant increase in the mitochondria membrane density,Fe2+,ROS and MDA levels,and p53 and ACSL4 protein expression levels(P<0.05).Conclusions:Brazilin actuated ferroptosis in breast cancer cells,and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.
