Glutathione, an Antioxidant Tripeptide: Dual Roles in Carcinogenesis and Chemoprevention

Abstract

Glutathione (GSH or reduced glutathione) is a tripeptide of gamma-Glutamyl-cysteinylglycine and the predominant intracellular antioxidant in many organisms including humans. GSH and associated enzymes are controlled by a transcription factor-nuclear factor-2 related erythroid factor-2 (Nrf2). In cellular milieu, GSH protects the cells essentially against a wide variety of free radicals including reactive oxygen species, lipid hydroperoxides, xenobiotic toxicants, and heavy metals. It has two forms, the reduced form or reduced glutathione (GSH) and oxidized form (GSSG), where two GSH moieties combine by sulfhydryl bonds. Glutathione peroxidase (GPx) and glutathione-s-transferase (GST) essentially perform the detoxification reactions using GSH, converting it into GSSG. Glutathione reductase (GR) operates the salvage pathway by converting GSSG to GSH with the expense of NADPH and restores the cellular GSH pool. Hence, GSH and GSH-dependent enzymes are necessary for maintaining the normal redox balance in the body and help in cell survival under stress conditions. In addition, GST removes various carcinogenic compounds offering a chemopreventive property, whereas the GSH system plays a significant role in regulating the cellular survival by offering redox stability in a variety of cancers including prostate, lung, breast, and colon cancer. Studies have also indicated that GSH inhibitors, such as buthionine sulfoximine, improve the chemo-sensitivity in cancer cells. In addition, GSH and dependent enzymes provide a survival advantage for cancer cells against chemotherapeutic drugs and radiotherapy.

Immunity Depletion, Telomere Imbalance, and Cancer-associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Caloric Restriction

“…However, GSH metabolism is associated with colorectal cancer pathogenesis (65). The GSH system regulates proliferation and survival by offering redox stability in a variety of cancers (66,67). MGST1 is crucial for stem differentiation (68).…”

The Relationship Between IgA Vasculitis and Antioxidant Activity In Children

“…Reduced glutathione (GSH) is the predominant intracellular antioxidant in many organisms. GSH protects cells against a wide variety of free radicals such as reactive oxygen species, lipid peroxides, xenobiotic toxins, and heavy metals 7 . Vitamin E (alpha-tocopherol), a natural antioxidant, neutralizes free radicals and protects the cell membrane against free oxygen radicals.…”

Docosahexaenoic acid inhibits the proliferation of Kras/TP53 double mutant pancreatic ductal adenocarcinoma cells through modulation of glutathione level and suppression of nucleotide synthesis

“…In most living organisms, intracellular redox homeostasis is mostly regulated by a balance between reduced glutathione (GSH) and oxidative glutathione (GSSG) [ 13 , 14 ]. In order to maintain cellular redox balance, conversion of GSSG to GSH takes place at the expense of NADPH [ 15 ]. GSH, an antioxidant tripeptide, consists of glycine, glutamine and cysteine [ 15 ].…”

“…In order to maintain cellular redox balance, conversion of GSSG to GSH takes place at the expense of NADPH [ 15 ]. GSH, an antioxidant tripeptide, consists of glycine, glutamine and cysteine [ 15 ]. The transsulfuration pathway is involved in providing cysteine and contributes to the synthesis of GSH [ 16 , 17 ].…”