The Role Caspase-8 and DNA Methylation in patients with Ovarian Cancer: Relationship with Oxidative Stress and Inflammation

Abstract

Background: Ovarian cancer (OC) is the most common cancer and a leading cause of death in women. It well known that suppress the apoptosis initiates tumor and its development. Oxidative stress, and inflammation showed to have a role in tumorigenesis. However, the mechanism still unclear. Methods: 90 females were involved in the current study. Blood samples were obtained from thirty healthy controls, thirty premenopausal women, and thirty postmenopausal women with primary diagnosis of ovarian cancer. Plasma SOD activity was determined by spectrophotometry method, plasma levels of 8-OHG, IL-8, and Cas-8 were measured by ELISA. methylation specific PCR (MSP PCR) was applied for measurements of un-methylation and methylation levels of Cas-8 gene. Result: The results showed a significant decrease in SOD activity in postmenopausal group compared to premenopausal women and control groups (P < 0.05). A significant increase in 8-OHG and IL-8 levels in both OC groups compared with control group (P < 0.05). Apoptosis were decreased through levels of Cas-8 in patients group compared to control group (P< 0.05). Also a high level methylation of Cas-8 gene was observed in plasma sample of patient groups compared to control group. Conclusions: low levels of Cas-8 and methylation of Cas-8 may be involved in OC carcinogenesis and consider as diagnostic marker. Oxidative stress-mediated inflammatory response and methylation of Cas-8, this may be for promoter hyper methylation in OC. Taken together, the result open new sight in strategy therapy for OC.