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

Motoki Takenaka,Hitomi Aoki,Ken-Ichirou Morishige,Tiger Koike,Noriko Suzuki,Tatsuro Furui

doi:10.4236/ojog.2022.121006

Abstract

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.

Highlights

The number of patients with ovarian cancer (OC) is increasing and deaths due to this disease are increasing in Japan [1]
Data showed that GSH might play roles in malignancy including ovarian cancer (OC), and, we attempted to determine the clinical significance of GSH and effects of erastin in OC
OC tissues were taken from 41 OC patients, and cancer-tissue GSH level was measured with GSH Assay Kit

Summary

Introduction

The number of patients with ovarian cancer (OC) is increasing and deaths due to this disease are increasing in Japan [1]. OC is generally sensitive to chemotherapy, most patients recur and develop resistance to chemotherapy [4] [5]. Survival rates are estimated based on previous outcomes [6], but it is not easy to predict what will happen in OC patients. Glutathione (GSH), an antioxidant, is used to mitigate the damage of reactive oxygen species (ROS) [7]. They have roles in cell cycle progression and cell death pathway. Erastin is a classical inhibitor that can lead to the depletion of GSH [8]

Objectives

Methods

Results