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 effect of different extracts of Lysimachiae Herba on the main toxicity induced by Tripterygii Radix et Rhizoma. Method:Ninety male SPF Kunming mice were randomly divided into 9 groups according to their body weight，control group， Lysimachiae Herba water extract group， Lysimachiae Herba 30% ethanol extract group， Tripterygii Radix et Rhizoma group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba water extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 30% ethanol extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 60% ethanol extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 95% ethanol extract group and Tripterygii Radix et Rhizoma combined with Lysimachiae Herba ethyl acetate extract group. The dosage of Tripterygii Radix et Rhizoma and Lysimachiae Herba were 2，1 g·kg<sup>-1</sup> based on crude drugs， respectively. The control group was given an equal volume of solvent， and each group was given by gavage for 14 consecutive days. The blood and liver tissues were taken 24 hours after the last administration. The enzyme linked immunosorbent assay （ELISA） was used to detect serum biochemical indexes and liver lipid peroxidation/antioxidant indexes in mice. Meanwhile， principal component analysis was used to evaluate the attenuating effect and the mechanism of Lysimachiae Herba extract on toxicity of Tripterygii Radix et Rhizoma. Result:Compared with control group， Tripterygii Radix et Rhizoma caused the levels of alanine aminotransferase（ALT），aspartic acid amino transferase（AST），alkaline phosphatase（ALP） in serum of mice， and the levels of malondialdehyde （MDA） in liver， and comprehensive score of toxicity （Z value） produced by the above four indexes increased significantly （<italic>P</italic><0.01）. The levels of total superoxide dismutase （T-SOD），glutathione-peroxidase （GPX），glutathione-S transferase （GST） decreased significantly （<italic>P</italic><0.01） in liver. Compared with Tripterygii Radix et Rhizoma group， after intervention with extracts of two solvents （water， 30% ethanol） of Lysimachiae Herba， the levels of serum ALT， AST， ALP and liver MDA were significantly decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the levels of liver T-SOD， GPX and GST were significantly increased （<italic>P</italic><0.01）. After intervention with extracts of two solvents （60% ethanol， 95% ethanol） of Lysimachiae Herba， the levels of serum ALT， AST， ALP were significantly decreased （<italic>P</italic><0.01）， and liver GPX levels were significantly increased （<italic>P</italic><0.01）. After the intervention with ethyl acetate extract of Lysimachiae Herba， only the level of serum AST was significantly decreased （<italic>P</italic><0.05） and the level of GPX was significantly increased （<italic>P</italic><0.05）. After the intervention with extracts of different solvents （water， 30% ethanol， 60% ethanol， 95% ethanol， ethyl acetate） of Lysimachiae Herba， it can significantly reduce the comprehensive score of toxicity （<italic>P</italic><0.01）. The overall decline rates of toxicity were 127.5%， 113.4%， 98.1%， 56.3% and 31.0% respectively. Among them， the toxicity reduction rate of the extracts with water as a solvent was 14.1%， 29.4%， 71.2%， 96.5% higher than those of other solvent extracts with ethanol. Conclusion:The extracts of different solvents （water， 30% ethanol， 60% ethanol， 95% ethanol and ethyl acetate） of Lysimachiae Herba can reverse the toxicity induced by Tripterygii Radix et Rhizoma in varying degrees. Among them， water and 30% ethanol are the best solvents for detoxification， especially water as the extraction solvent， and with the increase of ethanol content or fat solubility of extraction solvent， the detoxification shows a downward trend.
ABSTRACT
INTRODUCTION: In traditional society, the roles of housewives were to do housework, to look after her children and to give her family emotional stability. With rapid social and economic change, the traditional sense of value changes and the concepts of sexual roles, too. However, they are in a transition period yet. These discord and tension followed by role change appeared as the form of psychological instability or social pathological problem in modern family. Thus, this study aimed to avaluate the effect of employment on depression of housewives who play importent roles in family and their commumity. METHODS: From May to July 1996, the questonnaires were distributed to 179 housewives who have university education background(including community college), and have one or more children and live in Bundang-Ku of Sungnam city, making a distinction between working housewives and nonworking housewives. Regarding the subjects of this study, the non-working housewives are restricted to full-time housewives who have no job, and working housewives who have full-time job. As tools of measurement, we used BDI questionnaires consisted of 15 items in Korean. We performed statistical analysis among the data by means of SPSS/PC+. We analyzed statistical data for significance using one-way ANOVA and analyzed categorical data for significance using S-test. RESULTS: The average score on BDI for working housewives was 12.22(standard deviation 7.42) and this is rather higher than that of non-working housewives(10.80, standard deviation : 7.42). But the number of children increased, the BDI score were higher significantly in both groups. And the BDI score was high in working Housewives groups whose husbands had professional job or dommerce job, whose family system is a multi-generation family, and who feel a lot of fatigue after work. In case of non-working housewives, the BDI score was high with age(especially between 50-59), duration of marriage, lower income and Duvalls family life cycle 6, 7. CONCLUSIONS: There is no difference in depression tendency between working housewives and nonworking housewives. But in case of working housewives, some factors have influence on their depression tendency, the number of children, husbands job, family type, degree of fatigue after work. And in case of non-working housewives, the factors are the number of children, age, duration of marriage, income, family life cycle.