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
Chronic liver diseases can further develop to liver fibrosis and cirrhosis. Currently, there is no effective treatment except liver orthotopic transplantation at this point. The extreme shortage of liver organ source forced people to find alternative treatment strategies. Mesenchymal stem cells ( MSCs) have the abilities of immunomodulatory, hepatocyte differentiation, promotion of liver cells regeneration in situ and inhibiting the activation of hepatic stellate cells. Therefore, MSCs transplantation provides a very broad prospect for cell therapy. It is important to provide preclinical evaluation of the efficacy and safety before the application of cell therapy in clinical trials. The progress of various animal models of human liver diseasees and significance of using MSCs to treat liver diseases in preclincal studies based on these animal models were reviewed in this paper.