6533b826fe1ef96bd1283c75

RESEARCH PRODUCT

Glutathione in metastases: From mechanisms to clinical applications.

Angel OrtegaJosé M. EstrelaSalvador MenaElena ObradorJ. Antoni Sirerol

subject

0301 basic medicineProgrammed cell deathClinical BiochemistryCancer therapyOxidative phosphorylationBiologyGeneral Biochemistry Genetics and Molecular Biology03 medical and health scienceschemistry.chemical_compoundMice0302 clinical medicineMetastatic cellNeoplasmsmedicineAnimalsHumansNeoplasm MetastasisCarcinogenBiochemistry (medical)CancerGlutathionemedicine.diseaseGlutathione030104 developmental biologychemistry030220 oncology & carcinogenesisCancer cellImmunologyCancer research

description

Metastatic spread, not primary tumors, is the leading cause of cancer death. Glutathione (γ-glutamyl-cysteinyl-glycine, GSH) is particularly relevant in cancer cells as it is involved in regulating carcinogenic mechanisms, growth and dissemination, and multidrug and radiation resistance. Upon interaction of metastatic cells with the vascular endothelium, a high percentage of metastatic cells with high GSH levels survive the combined nitrosative and oxidative stresses elicited by the vascular endothelium. GSH release from different organs, mainly the liver, and its interorgan transport through the blood circulation to metastatic foci, promote their growth. This review focuses on the relationship among GSH and different key mechanisms that facilitate metastatic cell survival and growth, i.e. adaptive responses to stress, cell death evasion and utilization of physiological neuroendocrine mechanisms. Different strategies that are aimed at sensitizing metastases to cancer therapy by depleting metastatic cell GSH are analyzed.

10.3109/10408363.2015.1136259https://pubmed.ncbi.nlm.nih.gov/26754151