ABSTRACT
Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women. Lycium barbarum polysaccharide (LBP) is an extract from the fruits of the traditional Chinese herb, L. barbarum. LBP is a promising anticancer drug, due to its high activity and low toxicity. Although it has anticancer properties, its mechanisms of action have not been fully established. Ferroptosis, which is a novel anticancer strategy, is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species (ROS) accumulation. In this study, human breast cancer cells (Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast-231 (MDA-MB-231)) were treated with LBP. LBP inhibited their viability and proliferation in association with high levels of ferroptosis. Therefore, we aimed to ascertain whether LBP reduced cell viability through ferroptosis. We found that the structure and function of mitochondria, lipid peroxidation, and expression of solute carrier family 7 member 11 (SLC7A11, also known as xCT, the light-chain subunit of cystine/glutamate antiporter system Xc-) and glutathione peroxidase 4 (GPX4) were altered by LBP. Moreover, the ferroptosis inhibitor, Ferrostatin-1 (Fer-1), rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione (GSH) production, accumulation of intracellular free divalent iron ions and malondialdehyde (MDA), and down-regulation of the expression of xCT and GPX4. Erastin (xCT inhibitor) and RSL3 (GPX4 inhibitor) inhibited the expression of xCT and GPX4, respectively, which was lower after the co-treatment of LBP with Erastin and RSL3. These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the xCT/GPX4 pathway. Therefore, LBP exhibits novel anticancer properties by triggering ferroptosis, and may be a potential therapeutic option for breast cancer.
Subject(s)
Female , Humans , Breast Neoplasms/drug therapy , Drugs, Chinese Herbal/pharmacology , Ferroptosis , Glutathione/metabolism , Iron/metabolismABSTRACT
Objective To investigate the influence of glycyrrhizic acid (GA) on oxidative stress injury in glomerular mesangial cells (HBZY-1) induced high glucose.Methods HBZY-1 was cultured and divided into the normal control group,high glucose group and high glucose +-GA group.The cell proliferation activity was measured by MTT assay.UV spectrophotometry was used to detect the SOD and MDA levels.And the ROS changes were detected by laser confocal microscopy.Immunohistochemistry and Western blot were used to detect the expression of Mn-SOD protein in various groups.Mn-SOD mRNA was detected by Q-PCR.Results (1) The morphological changes in each group:HBZY-1 cells were diamond-shaped,cells were normal and the structure was clear in the NG group.In the HG+-GA group,the number of cells was increased slightly,individual cell body was slightly hypertrophy.The cell structure in the HG group was not clear,the cells appeared flat,the number was increased significantly,the cell body was slightly hypertrophy.(2)The proliferative effect of HBZY-1 in each group:compared with the NG group,the OD value in the HG group was significantly increased,and the OD value in the HG+GA group was decreased compared with the HG group(P＜0.05).(3)The relative content of ROS in the HG group was higher than that in the NG group,and which in the HG+GA group was decreased (P＜0.05).(4)The expression of Mn-SOD in each group:the relative expression of Mn-SOD in the HG group was significantly lower than that in the NG group (P＜0.05),and the expression of Mn-SOD in the HG+-GA group was increased compared with the HG group(P＜0.05).Conclusion Glycyrrhizic acid has a certain inhibiting effect on the abnormal proliferation of HBZY-1 induced by high glucose.Glycyrrhizic acid can protect the cell hypertrophy and cell damage caused by glomerular mesangial cells via oxidative stress,and glycyrrhizic acid can regulate the Mn-SOD expression induced by high glucose.
ABSTRACT
Objective To investigate the influence of glycyrrhizic acid (GA) on oxidative stress injury in glomerular mesangial cells (HBZY-1) induced high glucose.Methods HBZY-1 was cultured and divided into the normal control group,high glucose group and high glucose +-GA group.The cell proliferation activity was measured by MTT assay.UV spectrophotometry was used to detect the SOD and MDA levels.And the ROS changes were detected by laser confocal microscopy.Immunohistochemistry and Western blot were used to detect the expression of Mn-SOD protein in various groups.Mn-SOD mRNA was detected by Q-PCR.Results (1) The morphological changes in each group:HBZY-1 cells were diamond-shaped,cells were normal and the structure was clear in the NG group.In the HG+-GA group,the number of cells was increased slightly,individual cell body was slightly hypertrophy.The cell structure in the HG group was not clear,the cells appeared flat,the number was increased significantly,the cell body was slightly hypertrophy.(2)The proliferative effect of HBZY-1 in each group:compared with the NG group,the OD value in the HG group was significantly increased,and the OD value in the HG+GA group was decreased compared with the HG group(P＜0.05).(3)The relative content of ROS in the HG group was higher than that in the NG group,and which in the HG+GA group was decreased (P＜0.05).(4)The expression of Mn-SOD in each group:the relative expression of Mn-SOD in the HG group was significantly lower than that in the NG group (P＜0.05),and the expression of Mn-SOD in the HG+-GA group was increased compared with the HG group(P＜0.05).Conclusion Glycyrrhizic acid has a certain inhibiting effect on the abnormal proliferation of HBZY-1 induced by high glucose.Glycyrrhizic acid can protect the cell hypertrophy and cell damage caused by glomerular mesangial cells via oxidative stress,and glycyrrhizic acid can regulate the Mn-SOD expression induced by high glucose.
ABSTRACT
Aim To investigate the influence of gly-cyrrhizic acid( GA) on cell proliferation and cell cycle and secretion of extracellular matrix ( ECM) , the level of fibronection ( FN) , type Ⅳ collagen ( C-Ⅳ) in the rats′ glomerular mesangial cells ( HBZY-1 ) cultured with advanced glycation endproducts ( AGEs ) . Meth-ods HBZY-1 were incubated in culture medium con-taining AGEs in the presence of GA and treated for 48 h. At the same time, the normal and control groups were established. Methylthiazoletetrazolium ( MTT) as-say was used to measure cell proliferation;cell cycle a-nalysis was performed using a flow cytometry; FN and C-Ⅳwere analyzed by enzyme-linked immunosorbent assay ( ELISA ) . Results Cell counts increased markedly in AGEs group. Cell cycle analysis showed that cell percentage of S phase increased, G1 reduced and PI increased from 35. 01% ± 4. 21% to 44. 93%± 0. 25% ( P <0. 05 ) . FN and C-Ⅳ secretion in-creased ( P <0. 05 ) . Whereas GA was added, cell counts decreased, and the percentage of S phase also decreased and G1 increased, PI decreased from 44. 93% ± 0. 25% to 42. 16% ± 1. 04% ( P<0. 05 ) . In addition, the secretion of FN and C-Ⅳ decreased ( P<0. 05 ) . Conclusion GA could prevent AGEs-induced HBZY-1 . GA may protect HBZY-1 from in-hibiting the abnormal cell proliferation, changing the cell cycle. GA can reduce the synthesis of FN and C-Ⅳ.