Glutathione as a Prognostic Biomarker and a Potential Therapeutic Target for Ovarian Cancer

Aim: Glutathione (GSH) is an antioxidant, protecting cell against toxicity of reactive oxygen species (ROS). Data showed that GSH might play roles in malignancy including ovarian cancer (OC), and, thus, we attempted to determine the clinical significance of GSH and effects of erastin (an inhibitor of GSH synthesis) in OC. Methods: OC tissues were taken from 41 OC patients, and cancer-tissue GSH level was measured with GSH Assay Kit. Survival curves were carried out by the Kaplan-Meier method and evaluated using the log-rank test. Multivariable Cox proportional hazard risk regression model was performed to screen the independent factor affecting the prognosis of OC patients. In vitro effect of erastin was studied using OC cell lines. Cell viability, GSH levels and whole (cytosolic and lipid) ROS production were assessed. Results: Patients with high OC-tissue-GSH levels had an apparently lower progression free survival (PFS) and overall survival (OS) compared with those with low GSH levels. The GSH levels were independent factors for predicting the PFS and OS. The basal ROS level was inversely proportional to GSH levels in OC cell lines. The basal GSH levels were important for estimating the sensitivity to erastin. Reduction of intracellular GSH levels increased whole ROS, which caused cell deaths. Conclusions: Data suggested that the GSH levels could be a candidate of prognostic biomarkers and that erastin might be worth studying as a new therapeutic drug in OC.

Effects of cola intake on fertility: a review

The consumption of soft drinks has increased considerably during the last decades. Among them, the cola-based preparations are possibly the refreshments with the largest sales worldwide. During the previous years, important concerns have been raised about the effects of colas on human health. In this review, we introduce the cola effects on reproduction including pregnancy miscarriages, ovulatory and menstrual disorders, and reduced semen quality. Although caffeine intoxication may be thought to play the most important role, a component of cola other than caffeine, or in combination with caffeine, may be associated with increased risk of reproductive hazards in heavy cola (> 1 L per day)-consumers. Cola discontinuation usually leads to an uneventful recovery in the most cases suggesting justification of limitations in the maximum recommended daily dose of these soft drinks. Cola is not an essential beverage, and abstaining from drinking more than 1 L per day is a minor intrusion in one’s personal life. Despite these uncertainties, this growing know- ledge may alarm the fertility risk of chronic cola intake in peoples of childbearing age.

Role of Cathepsin G in the Degradation of Glyceraldehyde-3-Phosphate Dehydrogenase Triggered by 4-Hydroxy-2-Nonenal in U937 Cells

Degradation of oxidized or oxidatively modified proteins is an essential part of the cellular antioxidant defense system. 4-Hydroxy-2-nonenal (HNE), a major reactive aldehyde formed by lipid peroxidation, causes many types of cellular damage. HNE-modified proteins are degraded by the ubiquitin-proteasome pathway or the lysosomal pathway. However, our previous studies using U937 cells showed that HNE-modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is degraded by cathepsin G. In the present study, we examined whether GAPDH in U937 cells treated with HNE in culture is degraded similarly to that incubated with HNE and U937 cell extract. Treatment with HNE for 10 min in culture decreased GAPDH activity in a concentration dependent manner, but did not affect GAPDH degradation. The proteasome activities were not affected by HNE, but culturing with HNE decreased cathepsin G activity and protein level in a concentration dependent manner. These results suggest that HNE-induced oxidative stress leads to decreased cathepsin G activity and results in the loss of GAPDH degradation. Taken together, our findings indicate that cathepsin G has an important role in the degradation of oxidatively modified GAPDH in U937 cells.