Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells

Mj, Allalunis-Turner; Rs, Day; Jd, McKean; Kc, Petruk; Pb, Allen; Ke, Aronyk; Bk, Weir; Huyser-Wierenga, D; Ds, Fulton; Rc, Urtasun

doi:10.1007/bf02390175

Cited by 22 publications

(8 citation statements)

References 20 publications

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“…Moreover, indirect effects caused by the radiolysis of cellular water and the stimulation of oxidases result in GSH depletion and ROS generation ( 66 – 68 ) ( Table 2 and Figure 2 ). Studies have indicated that the efficacy of radiotherapy increases when GSH is depleted ( 69 , 70 ).…”

Section: The Role Of Ferroptosis In Mainstream Cancer Treatmentsmentioning

confidence: 99%

Ferroptosis in Cancer Treatment: Another Way to Rome

Luo

et al. 2020

Front. Oncol.

117

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Ferroptosis is a newly described type of programmed cell death and intensively related to both maintaining homeostasis and the development of diseases, especially cancers. Inducing ferroptosis leads to mitochondrial dysfunction and toxic lipid peroxidation in cells, which plays a pivotal role in suppressing cancer growth and progression. Here, we reviewed the existing studies about the molecular mechanisms of ferroptosis involved in different antitumor treatments, such as chemotherapy, targeted therapy, radiotherapy, and immunotherapy. We focused in particular on the distinct combinatorial therapeutic effects such as the synergistic sensitization effect and the drug-resistance reversal achieved when using ferroptosis inducers with conventional cancer therapy. Finally, we discussed the challenges and opportunities in clinical applications of ferroptosis. The application of nanotechnolgy and other novel technologies may provide a new direction in ferroptosis-driven cancer therapies.

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Section: The Role Of Ferroptosis In Mainstream Cancer Treatmentsmentioning

confidence: 99%

Ferroptosis in Cancer Treatment: Another Way to Rome

Luo

et al. 2020

Front. Oncol.

117

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“…From a therapeutic perspective, the increased GSH levels can also represent an enhanced ability of glioma cells to protect themselves from both radiation and chemotherapeutic agents (Dai et al ., 2007; Liu et al ., 2007). Thus, while not yet induced specifically by the inhibition of Sx c ‐ , depletion of GSH using the synthesis inhibitor l ‐ BSO rendered gliomas more sensitive to 1,3‐bis(2‐chloroethyl)‐1‐nitrosourea (BCNU)‐based chemotherapy and d ‐54 human glioma xenografts to radiotherapy (Lippitz et al ., 1990; Allalunis‐Turner et al ., 1991). Even greater attention has focused on the Sx c ‐ ‐mediated efflux of l ‐Glu from the glial tumours and its impact on brain tumour aetiology.…”

Section: Physiological and Pathological Rolesmentioning

confidence: 99%

System x_c^‐ cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS

Bridges

Natale

Patel

2011

British J Pharmacology

427

348

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System xc-is an amino acid antiporter that typically mediates the exchange of extracellular L-cystine and intracellular L-glutamate across the cellular plasma membrane. Studied in a variety of cell types, the import of L-cystine through this transporter is critical to glutathione production and oxidative protection. The exchange-mediated export of L-glutamate takes on added significance within the CNS, as it represents a non-vesicular route of release through which this excitatory neurotransmitter can participate in either neuronal signalling or excitotoxic pathology. When both the import of L-cystine and the export of L-glutamate are taken into consideration, system xc -has now been linked to a wide range of CNS functions, including oxidative protection, the operation of the blood-brain barrier, neurotransmitter release, synaptic organization, viral pathology, drug addiction, chemosensitivity and chemoresistance, and brain tumour growth. The ability to selectively manipulate system xc -, delineate its function, probe its structure and evaluate it as a therapeutic target is closely linked to understanding its pharmacology and the subsequent development of selective inhibitors and substrates. Towards that goal, this review will examine the current status of our understanding of system xc -pharmacology and the structure-activity relationships that have guided the development of an initial pharmacophore model, including the presence of lipophilic domains adjacent to the substrate binding site. A special emphasis is placed on the roles of system xc -within the CNS, as it is these actions that are among the most exciting as potential long-range therapeutic targets. Abbreviations4-S-CPG (S)-4-carboxyphenyglycine; 4-S-SPG, sulphonic acid phenylglycine; ACPA, amino-3-carboxy-5-methyl isoxazole propionic acid; trans-ACPD,1-aminocyclopentane-trans-1,3-dicarboxylic acid; ApcT, amino acid polyamine organo-cation transporter; ARE, antioxidant response element; ASC, alanine-serine-cysteine uptake systems; b-L-ODAP, L-b-N-oxalyl-L-a,b-diaminopropionate; BSO, buthionine sulphoximine; CPPG (R,S)-4-[4′-carboxyphenyl]-phenylglycine; dbcAMP, dibutyryl cyclic AMP; EAA, excitatory amino acid; EAAT, excitatory amino acid transporter; GSH, glutathione; HAT, heteromeric amino acid transporter family; iGluR, ionotropic glutamate receptor; KA, kainate; L-CysH, L-cysteine; L-Cys2, L-cystine; L-trans-2,4-PDC, L-trans-2,4-pyrrolidine dicarboxylate; mGluR, metabotropic glutamate receptor; NAC, N-acetyl-cysteine; NACPA, S-2-naphthyl-ethyl-ACPA; NEIH, 5-naphthylethyl isoxazole-4-(2,4-dinitrophenol)hydrazonedinitrophenol; Nrf2, nuclear factor erythroid-2-related factor; QA, quisqualate; ROS, reactive oxygen species; SAR, structure-activity-relationship; SLC, solute carrier gene families, SSZ, sulphasalazine, ) is an amino acid antiporter that typically mediates the exchange of extracellular L-cystine (L-Cys2) and intracellular L-glutamate (L-Glu) across the cellular plasma membrane. Initial characterizations of this transporter most often focus...

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“…The procedures used to dissociate the tumour specimens and to establish the cell lines have been previously published (Allalunis-Tumer et al, 1991). The M0059K cell line was derived from the biopsy of a grade IV astrocytoma with focal necrosis, vascular proliferation and occasional gemistocytes.…”

Section: Cell Linesmentioning

confidence: 99%

Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma xenografts: possible role of decreased oxygen consumption

Parliament¹,

Franko²,

Allalunis-Turner³

et al. 1997

Br J Cancer

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Summary In contrast to reports of extensive hypoxia in human gliomas in situ measured by P02 histography, non-invasive methods of assessing glioma oxygenation, including nitroimidazole binding, have yielded surprisingly contradictory results. In order to investigate the relationship of necrosis, hypoxia, nitroreductase activity and cellular respiration in human gliomas, subcutaneous models using the human glioma cell lines M059K, M006 and M01 Ob were developed in the murine SCID host. Intracranial growth of the M006 line was achieved in nude rats. The nitroreductive capacity of glioma cell lines was assessed and found to be similar to transplanted tumours previously reported in the literature. This suggests that if substantial numbers of viable hypoxic cells were present in situ in gliomas, then nitroimidazole-binding techniques should be capable of identifying them. Inter-tumour variability in the amount of necrosis was seen. M006 xenografts growing in subcutaneous and intracranial sites revealed extensive necrotic regions histologically, some of which were surrounded by cells labelled heavily for [3H]misonidazole, while other areas were lightly labelled. Similar binding patterns were seen for subcutaneous M059K tumours, while subcutaneous M01 Ob tumours display necroses of which almost all were surrounded by heavily labelled cells. The oxygen consumption rates of tumour cell lines grown in vivo, in which venous P02 concentrations are of the order of 2-5%, were two to sevenfold less than those of the same lines grown as monolayers in vitro under oxygen concentrations of 18%. We postulate that glioma cell lines behave as 'oxygen conformers', in that their rate of oxygen consumption appears to vary with the availability of oxygen. Together with the misonidazole-binding data, the results in this glioma tumour model are consistent with coordinate inhibition or down-regulation of respiration under moderate hypoxia.

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Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells

Cited by 22 publications

References 20 publications

Ferroptosis in Cancer Treatment: Another Way to Rome

Ferroptosis in Cancer Treatment: Another Way to Rome

System x_c^‐ cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS

Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma xenografts: possible role of decreased oxygen consumption

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Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells

Cited by 22 publications

References 20 publications

Ferroptosis in Cancer Treatment: Another Way to Rome

Ferroptosis in Cancer Treatment: Another Way to Rome

System xc‐ cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS

Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma xenografts: possible role of decreased oxygen consumption

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System x_c^‐ cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS