Role of Glutathione in Cancer Progression and Chemoresistance

Abstract

Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and disturbances in GSH homeostasis are involved in the etiology and progression of many human diseases including cancer. While GSH deficiency, or a decrease in the GSH/glutathione disulphide (GSSG) ratio, leads to an increased susceptibility to oxidative stress implicated in the progression of cancer, elevated GSH levels increase the antioxidant capacity and the resistance to oxidative stress as observed in many cancer cells. The present review highlights the role of GSH and related cytoprotective effects in the susceptibility to carcinogenesis and in the sensitivity of tumors to the cytotoxic effects of anticancer agents.

Chemotherapy triggers HIF-1–dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype

“…Glutathione is the major endogenous antioxidant produced by mammalian cells to detoxify free radicals. However, the role of glutathione in tumor initiation, cancer progression, and chemotherapy resistance has been controversial for many years, perhaps because glutathione may play both protective and pathogenic roles with respect to cancer (18,37). Recently it has been shown that inhibition of xCT or GCL by treatment with Fig.…”

“…The major antioxidant within cells is glutathione, a tripeptide that is synthesized from cysteine, glutamate, and glycine (18). Cystine is taken up by cells primarily through the xC(-) system, which is a heterodimeric protein consisting of a transporter subunit (xCT, encoded by the SLC7A11 gene) and a regulatory subunit (4F2hc, also known as CD98, encoded by the SLC3A2 gene) (19).…”

Multidrug Resistance-associated Protein-1 (MRP-1)-dependent Glutathione Disulfide (GSSG) Efflux as a Critical Survival Factor for Oxidant-enriched Tumorigenic Endothelial Cells

“…Arresting the glutathione and thioredoxin redox cycles has consistently provided productive returns in killing cancer cells (58,72,73). In oxidant-rich EOMA cells, intracellular GSSG levels are remarkably elevated.…”

Fluorescent Dyes Used in Polymer Carriers as Imaging Agents in Anticancer Therapy

“…The disulfide cleavage reactions have a great impact on chemical sensing of drug delivery involved in the polymer and pharmaceutical chemistry. The concentration of contrasting glutathione (GSH) inside cells and in plasma play an important role in the cellular antioxidant defense system and detoxification of reactive oxygen species [113,114]. The regulation of cellular redox status i.e., the equilibrium established between reduced free thiols (GSH) and oxidized disulfides (GSSG) is associated with a healthy condition and some kind of imbalance due to their abnormal levels are often related to diseases [115,116].…”