Glutathione Synthesis in Cancer Cells

Калинина, Е. В.; Gavriliuk, L A

doi:10.1134/s0006297920080052

Cited by 30 publications

(17 citation statements)

References 99 publications

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“…Glutathione (GSH) is a tripeptide and the main nonprotein sulfhydryl compound in cells, usually with varied concentrations of 0.5–10 mM. , The abnormal GSH concentration may indicate many diseases, such as Parkinson’s disease, cancer, and diabetes. − The chemical structure of GSH contains an active thiol group (−SH) which is easily oxidatively dehydrogenated, so it is a vital antioxidant to defend against oxidative stress and is related to many physiological and pathological processes. , GSH in cells is mainly in its reduced form (90–95%) instead of the oxidized form (GSSG) . Further, the content of GSH is often affected by the state of oxidative stress in cells, thereby reflecting their degrees of oxidative stress. , In cancerous cells, the GSH concentrations are often higher than that in normal cells, so it is important to develop an efficient method to determine the cellular GSH level for tumor diagnosis and other biomedical applications .…”

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confidence: 99%

“…6,7 GSH in cells is mainly in its reduced form (90−95%) instead of the oxidized form (GSSG). 8 Further, the content of GSH is often affected by the state of oxidative stress in cells, thereby reflecting their degrees of oxidative stress. 9,10 In cancerous cells, the GSH concentrations are often higher than that in normal cells, so it is important to develop an efficient method to determine the cellular GSH level for tumor diagnosis and other biomedical applications.…”

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confidence: 99%

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Glutathione Content Detection of Single Cells under Ingested Doxorubicin by Functionalized Glass Nanopores

Zhang

Wang

et al. 2021

Anal. Chem.

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Glutathione (GSH) level in cells maintains redox homeostasis, so the detection of intracellular GSH is crucial for many pathological processes. In the present study, we developed a cystaminefunctionalized glass nanopore (cG-nanopore) for the specific detection of GSH in single cells through the Michael addition reaction between the amino group of cystamine and polydopamine adhered to the inner wall of the glass nanopore. The cellular GSH will cleave the disulfide bond of cystamine and induce a negative charge increase on the residual surface of the modified nanopore, thus producing a sensitive response on the current−voltage curves. The developed sensing platform showed a good response relationship with the GSH concentration and an excellent selectivity against interfering substances in cells. The variation of GSH content in single HeLa and H8 cells incubated with DOX was then further quantified by this method.

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confidence: 99%

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confidence: 99%

Glutathione Content Detection of Single Cells under Ingested Doxorubicin by Functionalized Glass Nanopores

Zhang

Wang

et al. 2021

Anal. Chem.

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“…The ratio of GSH and GSSG provides insight into the extent of glutathione against oxidative stress and is often used as a marker of cytotoxicity. Studies have demonstrated the importance of GSH and GSH/GSSG ratios in regulating tumor cell viability, tumor development, progression, and initiation of drug resistance (Huang et al, 2001;Kalinina and Gavriliuk, 2020). Furthermore, glutathione is an important signaling controller of cellular differentiation, proliferation, apoptosis, ferroptosis and immune function (Kennedy et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Cell metabolomics study on the anticancer effects of Ophiopogon japonicus against lung cancer cells using UHPLC/Q-TOF-MS analysis

Shen

Hong

et al. 2022

Front. Pharmacol.

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Ophiopogon japonicus (OJ) is a traditional Chinese herbal medicine that has been used for thousands of years. Recently, the anticancer effects of OJ have been reported in multiple types of cancer, particularly in lung cancer. However, the underlying mechanisms remain unclear. In present study, the effects of OJ against NCI-H1299 human lung cancer cells were investigated, and the underlying mechanisms were explored using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS)-based cell metabolomics. As a result, OJ inhibited the proliferation, induced the apoptosis and suppressed the migration of NCI-H1299 cells. A total of 22 differential metabolites responsible for the effects of OJ were screened and annotated based on the LC-MS-based cell metabolomics approach. The altered metabolites were involved in three metabolic pathways, including glycerophospholipid metabolism, ether lipid metabolism and glutathione metabolism. These results showed that cell metabolomics-based strategies are promising tools to discover the action mechanisms of OJ against lung cancer cells.

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“…As GSH metabolism plays an important role in multiple cancers (22,23), and GSH depletion induces ferroptosis (13), we explored the effect of circP4HB on ferroptosis. First, to clarify whether ferroptosis is implicated in LUAD, we examined cellular ferroptosis by adding erastin to the culture media of different LUAD cell lines (A549, SPCA1, H1299, H358) and in the normal bronchial epithelial cell line, 16HBE cells.…”

Section: Circp4hb Inhibits Ferroptosis In Luad Cells From By Promotin...mentioning

confidence: 99%

CircP4HB regulates ferroptosis via SLC7A11-mediated glutathione synthesis in lung adenocarcinoma

Pan¹,

Wei²,

Ma³

et al. 2022

Transl Lung Cancer Res

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Background: Circular ribonucleic acids (circRNAs) play a key role in the development of different types of cancer. Ferroptosis is a type of programmed cell death that contributes to cancer progression. However, the role of circRNAs in lung adenocarcinoma (LUAD) ferroptosis remains unclear. Methods:The gene expression levels of circRNA P4HB (circP4HB), microRNA-1184 (miR-1184) and Solute carrier family 7 member 11 (Slc7a11), also known as Xct were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Ferroptosis of established LUAD cells was induced by erastin.Cell viability was examined via Cell Counting Kit 8 assays. Ferroptosis was evaluated by malondialdehyde (MDA), Prostaglandin-endoperoxide Synthase 2 (Ptgs2), lipid reactive oxygen species (lipid ROS), and JC-1 detection. The mechanism of circP4HB/miR-1184/SLC7A11 was investigated by luciferase reporter assays, RNA immunoprecipitation, RNA pull-down, and western blot assays. A functional for circP4HB in vivo was determined using xenograft nude mice models.Results: CircP4HB expression levels were increased in LUAD. It triggered glutathione (GSH) synthesis and, therefore protected LUAD cells from ferroptosis induced by erastin. CircP4HB may function as a competing endogenous RNA by modulating miR-1184 to regulate SLC7A11. CircP4HB inhibited ferroptosis by regulating miR-1184/ SLC7A11-mediated GSH synthesis. In vivo, overexpression of circP4HB promoted tumor growth and inhibited ferroptosis. Conclusions:The circRNA, circP4HB acts as a novel ferroptosis suppressor in LUAD. Furthermore, circP4HB protects LUAD from ferroptosis via modulation of the miR-1184/SLC7A11 axis. Our findings identified circP4HB as a novel biomarker in LUAD and warrants further investigation in the early diagnosis and treatment of LUAD.

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Glutathione Synthesis in Cancer Cells

Cited by 30 publications

References 99 publications

Glutathione Content Detection of Single Cells under Ingested Doxorubicin by Functionalized Glass Nanopores

Glutathione Content Detection of Single Cells under Ingested Doxorubicin by Functionalized Glass Nanopores

Cell metabolomics study on the anticancer effects of Ophiopogon japonicus against lung cancer cells using UHPLC/Q-TOF-MS analysis

CircP4HB regulates ferroptosis via SLC7A11-mediated glutathione synthesis in lung adenocarcinoma

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