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Cysteine Depletion, a Key Action to Challenge Cancer Cells to Ferroptotic Cell Death.
Front Oncol. 2020; 10:723.FO

Abstract

Cancer cells are characterized as highly proliferative at the expense of enhancement of metabolic rate. Consequently, cancer cells rely on antioxidant defenses to overcome the associated increased production of reactive oxygen species (ROS). The reliance of tumor metabolism on amino acids, especially amino acid transport systems, has been extensively studied over the past decade. Although cysteine is the least abundant amino acid in the cell, evidences described it as one of the most important amino acid for cell survival and growth. Regarding its multi-functionality as a nutrient, protein folding, and major component for redox balance due to its involvement in glutathione synthesis, disruption of cysteine homeostasis appears to be promising strategy for induction of cancer cell death. Ten years ago, ferroptosis, a new form of non-apoptotic cell death, has been described as a result of cysteine insufficiency leading to a collapse of intracellular glutathione level. In the present review, we summarized the metabolic networks involving the amino acid cysteine in cancer and ferroptosis and we focused on describing the recently discovered glutathione-independent pathway, a potential player in cancer ferroptosis resistance. Then, we discuss the implication of cysteine as key player in ferroptosis as a precursor for glutathione first, but also as metabolic precursor in glutathione-independent ferroptosis axis.

Authors+Show Affiliations

Medical Biology Department, Centre Scientifique de Monaco (CSM), Monaco, Monaco.Medical Biology Department, Centre Scientifique de Monaco (CSM), Monaco, Monaco.Medical Biology Department, Centre Scientifique de Monaco (CSM), Monaco, Monaco. Institute for Research on Cancer and Aging (IRCAN), CNRS, INSERM, Centre A. Lacassagne, Université Côte d'Azur, Nice, France.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32457843

Citation

Daher, Boutaina, et al. "Cysteine Depletion, a Key Action to Challenge Cancer Cells to Ferroptotic Cell Death." Frontiers in Oncology, vol. 10, 2020, p. 723.
Daher B, Vučetić M, Pouysségur J. Cysteine Depletion, a Key Action to Challenge Cancer Cells to Ferroptotic Cell Death. Front Oncol. 2020;10:723.
Daher, B., Vučetić, M., & Pouysségur, J. (2020). Cysteine Depletion, a Key Action to Challenge Cancer Cells to Ferroptotic Cell Death. Frontiers in Oncology, 10, 723. https://doi.org/10.3389/fonc.2020.00723
Daher B, Vučetić M, Pouysségur J. Cysteine Depletion, a Key Action to Challenge Cancer Cells to Ferroptotic Cell Death. Front Oncol. 2020;10:723. PubMed PMID: 32457843.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cysteine Depletion, a Key Action to Challenge Cancer Cells to Ferroptotic Cell Death. AU - Daher,Boutaina, AU - Vučetić,Milica, AU - Pouysségur,Jacques, Y1 - 2020/05/07/ PY - 2020/02/21/received PY - 2020/04/16/accepted PY - 2020/5/28/entrez PY - 2020/5/28/pubmed PY - 2020/5/28/medline KW - cysteine KW - ferroptosis KW - glutathione KW - lipid peroxides KW - tumor-resistance KW - xCT transporter SP - 723 EP - 723 JF - Frontiers in oncology JO - Front Oncol VL - 10 N2 - Cancer cells are characterized as highly proliferative at the expense of enhancement of metabolic rate. Consequently, cancer cells rely on antioxidant defenses to overcome the associated increased production of reactive oxygen species (ROS). The reliance of tumor metabolism on amino acids, especially amino acid transport systems, has been extensively studied over the past decade. Although cysteine is the least abundant amino acid in the cell, evidences described it as one of the most important amino acid for cell survival and growth. Regarding its multi-functionality as a nutrient, protein folding, and major component for redox balance due to its involvement in glutathione synthesis, disruption of cysteine homeostasis appears to be promising strategy for induction of cancer cell death. Ten years ago, ferroptosis, a new form of non-apoptotic cell death, has been described as a result of cysteine insufficiency leading to a collapse of intracellular glutathione level. In the present review, we summarized the metabolic networks involving the amino acid cysteine in cancer and ferroptosis and we focused on describing the recently discovered glutathione-independent pathway, a potential player in cancer ferroptosis resistance. Then, we discuss the implication of cysteine as key player in ferroptosis as a precursor for glutathione first, but also as metabolic precursor in glutathione-independent ferroptosis axis. SN - 2234-943X UR - https://www.unboundmedicine.com/medline/citation/32457843/Cysteine_Depletion,_a_Key_Action_to_Challenge_Cancer_Cells_to_Ferroptotic_Cell_Death L2 - https://doi.org/10.3389/fonc.2020.00723 DB - PRIME DP - Unbound Medicine ER -
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