TITLE:
Glutathione as a Prognostic Biomarker and a Potential Therapeutic Target for Ovarian Cancer
AUTHORS:
Motoki Takenaka, Tatsuro Furui, Noriko Suzuki, Tiger Koike, Hitomi Aoki, Ken-Ichirou Morishige
KEYWORDS:
Glutathione, Reactive Oxygen Species, Ovarian Cancer, Erastin
JOURNAL NAME:
Open Journal of Obstetrics and Gynecology,
Vol.12 No.1,
January
24,
2022
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.