The role of glutathione in brain tumor drug resistance

Backos, Donald S.; Franklin, Christopher C.; Reigan, Philip

doi:10.1016/j.bcp.2011.11.016

Cited by 155 publications

(106 citation statements)

References 115 publications

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“…The mechanisms of drug resistance involve, but are not limited to, the following aspects: The impairment of the DNA repair ability (18), the enrichment of P-glycoprotein (19), the glutathione transferase promotion of the metabolism of anticancer medicine (20) and the existence of CSCs (21). In the present study, the existence of CSCs in drug resistance was preliminarily evaluated.…”

Section: Discussionmentioning

confidence: 98%

Spheres from cervical cancer cells display stemness and cancer drug resistance

Liu

Wang

et al. 2016

Oncology Letters

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Abstract. Cervical cancer is one of the most common gynecological malignant tumors and is the cause of a serious health problem worldwide. An increasing amount of evidence has shown that cancer stem cells (CSCs) are present in tumors, and that these CSCs may be responsible for tumor metastasis and relapse. The present study aimed to identify and characterize a CSC population from the CaSki cell line. First, a stem cell culture medium was used to selectively expand the cancer stem-like cell spheres, and the putative stemness markers, Oct4 and Sox2, were identified. These markers were all highly expressed in the CaSki sphere-forming cells. Next, target region amplified polymorphism-polymerase chain reaction was performed and the CaSki sphere-forming cells were found to exhibit higher telomerase activity than the CaSki control cells cultured in non-stem cell medium. Using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, it was found that the CaSki sphere-forming cells were more resistant to chemotherapeutic drugs than the control CaSki cells. Using the tumor invasive assay, it was shown that the CaSki sphere-forming cells were more invasive than the control CaSki cells. These characteristics all suggested that the tumor sphere-forming cells mirrored the acknowledged CSC phenotypes. Overall, the use of a suspended sphere culture of CaSki cells may be an easy and feasible approach for enriching cancer stem-like cells in cervical cancer research.

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Section: Discussionmentioning

confidence: 98%

Spheres from cervical cancer cells display stemness and cancer drug resistance

Liu

Wang

et al. 2016

Oncology Letters

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“…Cumulative evidence has established the importance of GSTs as determinants of therapeutic response and survival in patients with cancer (33)(34)(35). The aim of the present study is to investigate whether GST-M2 participates in the cell migration process in NSCLCs, by evaluating the CCN2 pathway, a key signaling system that controls migratory responses in lung cancer.…”

Section: Introductionmentioning

confidence: 98%

Glutathione S-Transferase Mu2 Suppresses Cancer Cell Metastasis in Non–Small Cell Lung Cancer

Tang

Lai

et al. 2013

Molecular Cancer Research

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Glutathione S-transferase mu2 (GST-M2) is a phase II detoxification enzyme. Low expression of GST-M2 in lung cancers is due to hypermethylation of its promoter. Lung cancer with the GST mu-null genotype is associated with shorter survival. However, a correlation between GST-M2 and important clinical parameters, as well as the migration of GST-M2-defective cells in lung cancer, has not been established. In the present study, we investigate the role of GST-M2 in cell migration and actin disassembly in lung cancer cells. GST-M2 and CCN2 mRNA levels were significantly reduced in non-small cell lung cancer (NSCLC) tumors when compared with matched normal lung tissues in 82 patients with NSCLC. We found that high expressions of both GST-M2 and CCN2 are correlated with favorable survival of patients with lung cancer when compared with similar patients without GST-M2 or CCN2 expression. GST-M2 can induce CCN2 expression by driving the CCN2 proximal promoter. Overexpression of GST-M2 decreases the formation of filopodia, resulting in remodeling of the reorganized cytoskeletons. Overexpression of GST-M2 significantly suppressed cancer cell migration on wound-healing assay. In addition, overexpression of GST-M2 dramatically reduced tumor growth and metastasis in a xenograft mouse model. These data highlight the potential of GST-M2 as a novel tumor suppressor. GST-M2 increases the expression of CCN2 in lung cancer cells, which inhibits cancer cell migration in lung cancer and animal models. Mol Cancer Res; 11(5); 518-29. Ó2013 AACR.

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“…GSH in the brain plays a crucial role in maintaining the redox homeostasis in both glial and neuronal cell types [4]. The assessment of the level of GSH in the brain may be useful in studies of the role of glutathione in brain tumor drug resistance [5] or in studies of the possible role of antioxidants as neuroprotective therapeutic strategies for some mental illness [6]. A number of factors including neurodegenerative diseases may affect the changes in GSH and GSSG levels in the brain [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Optimization of determination of reduced and oxidized glutathione in rat striatum by HPLC method with fluorescence detection and pre-column derivatization

Krzyżanowska¹,

Gawlik²,

Filip³

2014

Acta Chromatographica

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Summary.A high-performance liquid chromatography (HPLC) method was used to assess the concentration of reduced and oxidized glutathione (GSH and GSSG) in rat striatum. Following decapitation, striatum was isolated from the male Wistar rat brain and immediately homogenized with double distilled water. GSH level was determined after pre-column derivatization with o-phthalaldehyde (OPA). The optimal incubation time with OPA was tested. The concentration of GSSG was determined after blockage the thiol groups of GSH by N-ethylmaleimide (NEM). The useful time for incubation with NEM was optimized. Next, disulfide bounds of GSSG were reduced by dithiothreitol (DTT), and released GSH is derivatized with OPA. The total glutathione, tGSH (sum of free and bound GSH, GSSG, and other low-molecular-mass aminothiols), was determined after reduction with DTT and then derivatization with OPA. The level of GSSG was calculated of the difference in concentrations of tGSH and GSH, but we showed that the calculated concentration of GSSG was within the range of standard deviation of the mean concentration of tGSH or GSH. Finally, the concentration of GSH was determined after 5-min incubation with OPA and the concentration of GSSG after 30-s incubation with NEM and 5-min incubation with DTT and OPA. The relative standard deviation (RSD) values obtained for the assay of GSH and GSSG were lower than 10%. The values obtained for accuracy for GSH (50-500 nM) and GSSG (0.5-5 nM) were within limits regarded as acceptable for analysis of biological samples (percent of recovery: 95-105%). Mean absolute recovery of GSH and GSSG was ranged from 97.1% to 99%. Limit of detection for GSH was 2.7 nM, and limit of quantification was 8.2 nM. Limit of detection (LOD) for GSSG is twice the value for GSH. Described method allows to determine GSH and GSSG levels in isolated rat brain structures with high level of reliability.

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The role of glutathione in brain tumor drug resistance

Cited by 155 publications

References 115 publications

Spheres from cervical cancer cells display stemness and cancer drug resistance

Spheres from cervical cancer cells display stemness and cancer drug resistance

Glutathione S-Transferase Mu2 Suppresses Cancer Cell Metastasis in Non–Small Cell Lung Cancer

Optimization of determination of reduced and oxidized glutathione in rat striatum by HPLC method with fluorescence detection and pre-column derivatization

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