Abstract
Glutathione (GSH) has several roles in a cell, such as a reactive oxygen species (ROS) scavenger, an intervenient in xenobiotics metabolism and a reservoir of cysteine. All of these activities are important in the maintenance of normal cells homeostasis but can also constitute an advantage for cancer cells, allowing disease progression and resistance to therapy. Ovarian cancer is the major cause of death from gynaecologic disease and the second most common gynaecologic malignancy worldwide. In over 50 years, the overall survival of patients diagnosed with epithelial ovarian cancer has not changed, regardless of the efforts concerning early detection, radical surgery and new therapeutic approaches. Late diagnosis and resistance to therapy are the main causes of this outcome, and GSH is profoundly associated with chemoresistance to platinum salts, which, together with taxane-based chemotherapy and surgery, are the main therapy strategies in ovarian cancer treatment. Herein, we present some insights into the role of GSH in the poor prognosis of ovarian cancer, and also point out how some strategies underlying the dependence of ovarian cancer cells on GSH can be further used to improve the effectiveness of therapy.
Highlights
In 1888, Rey-Pailhade described philothion, a molecule that reacted spontaneously with sulphur, producing hydrogen sulphide [1,2]
Hopkins concluded that philothion and glutathione (GSH) were identical and, after several studies, in 1935, its structure was established as a tripeptide, composed of glutamic acid, cysteine and glycine [1,3]
The first enzyme catalyses the formation of a dipeptide bond between the γ-carboxylate of glutamic acid and the amino group of cysteine and the latter catalyses the subsequent formation of a peptide bond between the cysteinyl carboxylate of γ-Glu–Cys and the amino group of glycine
Summary
In 1888, Rey-Pailhade described philothion, a molecule that reacted spontaneously with sulphur, producing hydrogen sulphide [1,2]. Radiotherapy is not commonly used to treat ovarian cancer As it plays so many important roles in cell biology, the linkage of GSH deregulation with disease is obvious. We will review the role of GSH in cancer, focusing on ovarian cancer, the major cause of death from gynaecologic disease and the second most common gynaecologic malignancy worldwide [20,21]. This molecule is profoundly associated with platinum salt resistance, one of the main treatment strategies for ovarian cancer, and is of extreme importance as a potential threat to ovarian cancer cells
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