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Glutathione in Cancer Cell Death
Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia, Spain
Green Molecular SL, Pol. Ind. La Coma-Parc Cientific, 46190 Paterna, Valencia, Spain
* Author to whom correspondence should be addressed.
Received: 30 December 2010; in revised form: 22 February 2011 / Accepted: 9 March 2011 / Published: 11 March 2011
Abstract: Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy.
Keywords: glutathione; cancer; cell death; apoptosis; necrosis; autophagy
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MDPI and ACS Style
Ortega, A.L.; Mena, S.; Estrela, J.M. Glutathione in Cancer Cell Death. Cancers 2011, 3, 1285-1310.
Ortega AL, Mena S, Estrela JM. Glutathione in Cancer Cell Death. Cancers. 2011; 3(1):1285-1310.
Ortega, Angel L.; Mena, Salvador; Estrela, Jose M. 2011. "Glutathione in Cancer Cell Death." Cancers 3, no. 1: 1285-1310.