Reactive Oxygen Species and Serous Epithelial Ovarian Adenocarcinoma.

Shakeria Cohen

doi:10.11648/j.crj.20160406.13

Abstract

Serous ovarian cancer (SOC) is usually diagnosed at late stage and stage-adjusted five year survival rate is low. Mortality is relatively heavy on African-Americans/Black (AA) affected with SOC compared to their Caucasian counterparts, though the cause for the disparity remains unclear. DNA damage induced by oxidative stress has been linked to ovarian cancer, but the role of oxidative stress in distinguishing differences in aggressive SOC tumors among patients is yet to be determined. This study aims to determine the levels of reactive oxygen species (ROS), malondialdehyde (MDA), reactive carbonyl groups and antioxidants in primary SOC normal, precancerous (cystadenoma, borderline) and invasive (III/IV) tissue samples obtained from AA and Caucasian subgroups. Additionally, the study seeks to investigate significant changes in the level of ROS between AA and Caucasian SOC samples. A fluorogenic probe, dichlorodihydrofluorescein (DCFH-DiOxyQ), was used to scavenge reactive oxygen species in SOC normal, precancerous and malignant stages III/IV tissue samples. Malondialdehyde (MDA), a lipid peroxidation marker, and reactive carbonyl groups were measured as indicators of oxidative injury. Moreover, antioxidant status was assessed by estimating glutathione peroxidase 3 (GPX3) enzyme levels. Results indicate ROS concentration was approximately 96% higher in the malignant tissues in comparative to the normal non-diseased controls. In addition, ROS concentration among AA women was approximately 9% higher than Caucasian women. MDA levels increased exponentially from non-disease control and precancerous tissues relative to malignant tissues. Furthermore, malignant serous ovarian samples showed significantly higher reactive carbonyl content compared to the non-disease controls (p=0.009), while GPX3 levels decreased considerably in serous cystadenoma and malignant tissue samples, and non-diseased control compared to borderline disease. The results suggest accumulation of ROS and MDA levels may be a causative factor for SOC. Elevated levels of MDA and reactive carbonyl proteins could override the GPX3 enzyme capacity therefore, initiating serous ovarian neoplasm.

Highlights

Ovarian cancer represents the fifth most frequent cause of cancer mortality among American women, and is by far the most aggressive form of malignancy affecting the female reproductive tract [1,2,3]
There was not substantial difference shown in reactive oxygen species (ROS) among serous cystadenoma and borderline tissue samples, when compared to malignant samples, there was a noticeable increase of 33% and 24% levels of the reactive compounds respectively (Figure 1)
The present study has shown an association between higher levels of ROS, MDA adducts and reactive carbonyl proteins among serous ovarian invasive tumor samples as compared to cystadenomas, borderline and normal specimens that are statistically significant

Summary

Introduction

Ovarian cancer represents the fifth most frequent cause of cancer mortality among American women, and is by far the most aggressive form of malignancy affecting the female reproductive tract [1,2,3]. A recent study evaluating serum of SOC patient samples, found glutathione peroxidase 3 enzyme to be extremely lower in patients suffering with malignant stages III/IV and recurrent disease [11] not in cystadenoma and borderline patient samples. An epidemiological study reported a correlation between borderline and malignant epithelial ovarian tumors [12]. Based on these observations, it is logical to speculate the biochemical and molecular changes caused by elevated ROS could be involved in the tumorigenesis of SOC. We evaluate levels of ROS stress against antioxidant enzyme, glutathione peroxidase 3 (GPX3) in normal and precancerous (cystadenoma, borderline) SOC tissues in association with malignant stages III & IV samples obtained from AA and Caucasian subgroups

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