Glutathione and redox-dependent regulation under the cancer cell drug resistance to cisplatin

Construction of Genetically Encoded Biosensors to Monitor Subcellular Compartment-Specific Glutathione Response to Chemotherapeutic Drugs in Acute Myeloid Leukemia Cells

“…It modulates various cellular processes, such as cell signaling pathways, metabolism, defense, proliferation, stress response, and detoxification of oxidants . The significance of the GSH/GSSG ratio in tumor growth, progression, and drug resistance has been highlighted . In different types of cancers, GSH-mediated oxidative stress has been reported as a plausible therapeutic target for most drugs.…”

“…In addition, leukemic cells exhibit a decline in reduced GSH and an increase in oxidized glutathione (GSSG) levels, indicating that AML cells are hypersensitive to chemotherapeutic drug-mediated inhibition of GSH metabolism . Moreover, the mechanism underlying the development of cancer cell resistance to therapeutic drugs is based on the overexpression of glutamate–cysteine ligase (GCL, GCLC) and glutathione synthetase (GSS) involved in GSH synthesis, leading to an increase in GSH/GSSG . Thus, it is important to measure the intracellular GSH/GSSG ratio in AML.…”

“… 7 The significance of the GSH/GSSG ratio in tumor growth, progression, and drug resistance has been highlighted. 8 In different types of cancers, GSH-mediated oxidative stress has been reported as a plausible therapeutic target for most drugs. For example, in AML, there is an increased expression of numerous glutathione pathway regulatory proteins to combat oxidative stress.…”

“… 4 Moreover, the mechanism underlying the development of cancer cell resistance to therapeutic drugs is based on the overexpression of glutamate–cysteine ligase (GCL, GCLC) and glutathione synthetase (GSS) involved in GSH synthesis, leading to an increase in GSH/GSSG. 8 Thus, it is important to measure the intracellular GSH/GSSG ratio in AML. GSH is found in various subcellular compartments, such as the mitochondria, cytosol, nucleus, and endoplasmic reticulum (ER), and its concentration varies significantly in different organelles.…”