Microsomal glutathione transferase 1 in anticancer drug resistance

Johansson, Katarina; Åhlen, Karin; Rinaldi, Rosanna; Sahlander, Karin; Siritantikorn, Atchasai; Morgenstern, Ralf

doi:10.1093/carcin/bgl148

Cited by 50 publications

(57 citation statements)

References 32 publications

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“…Their results revealed that high expression of MGST1 is significantly associated with DOX-resistance in patients with Ewing sarcoma during chemotherapy. It was reported that several anticancer drugs were definitely substrates for MGSTs, including melphalan and chlorambucil (CMB) (Johansson et al, 2007), and these drugs can activate MGST by reacting with Cys49 in MGST, thus facilitating its conjugation with GSH. Transporters, especially MRP1 and MRP2, show higher transport velocities (V max values) for the exertion of GSH-conjugated drug, which decreases the concentration of them in cancer cells and results in acquired drug resistance.…”

Section: Gstsmentioning

confidence: 99%

Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters

Bai

Chen

Hou

et al. 2016

Drug Metabolism Reviews

137

105

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Chemoresistance is a disturbing barrier in cancer therapy, which always results in limited therapeutic options and unfavorable prognosis. Nuclear factor E2-related factor 2 (NRF2) controls the expression of genes encoding cytoprotective enzymes and transporters that protect against oxidative stress and electrophilic injury to maintain intrinsic redox homeostasis. However, recent studies have demonstrated that aberrant activation of NRF2 due to genetic and/or epigenetic mutations in tumor contributes to the high expression of phase I and phase II drug-metabolizing enzymes, phase III transporters, and other cytoprotective proteins, which leads to the decreased therapeutic efficacy of anticancer drugs through biotransformation or extrusion during chemotherapy. Therefore, a better understanding of the role of NRF2 in regulation of these enzymes and transporters in tumors is necessary to find new strategies that improve chemotherapeutic efficacy. In this review, we summarized the recent findings about the chemoresistance-promoting role of NRF2, NRF2-regulated phase I and phase II drug-metabolizing enzymes, phase III drug efflux transporters, and other cytoprotective genes. Most importantly, the potential of NRF2 was proposed to counteract drug resistance in cancer treatment.

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Section: Gstsmentioning

confidence: 99%

Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters

Bai

Chen

Hou

et al. 2016

Drug Metabolism Reviews

137

105

View full text Add to dashboard Cite

show abstract

“…Our result showed a significant increased(p<0.001) activity of GSTs in stage-III (received chemotherapy) than stage-II patients (TABLE 3).Many studies also showed progressive increase of GSTs with advancing cancer and has been associated with poor prognosis and development of drug resistance [11][12][13].K.Johansson et al [13] reported GSTs protect the cells from lipid peroxidation and H2O2which is increased by cisplastin, a chemotherapeutic drug .Our results show the association of serum GST and chemotherapy in oesophagus cancer.…”

Section: Discussionmentioning

confidence: 68%

Clinical utility of glutathione-S-transferases, Alkaline Phosphatase and Lactate Dehydrogenase activity in oesophagus cancer patients before and after chemotherapy for Diagnosis and Prognosis

Ambad¹,

Jape²,

Nagtilak³

2014

IOSRJDMS

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“…Expression of microsomal glutathione S-transferase (MGST) has been shown to confer resistance to cisplatin [22]. In this analysis, expression of MGST1 [224918_x_at] increased with passage in several cell lines such as LOX IMVI and NCI-H226.…”

Section: Resultsmentioning

confidence: 96%

Gene expression profiling of 49 human tumor xenografts from in vitro culture through multiple in vivo passages - strategies for data mining in support of therapeutic studies

et al. 2014

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BackgroundDevelopment of cancer therapeutics partially depends upon selection of appropriate animal models. Therefore, improvements to model selection are beneficial.ResultsForty-nine human tumor xenografts at in vivo passages 1, 4 and 10 were subjected to cDNA microarray analysis yielding a dataset of 823 Affymetrix HG-U133 Plus 2.0 arrays. To illustrate mining strategies supporting therapeutic studies, transcript expression was determined: 1) relative to other models, 2) with successive in vivo passage, and 3) during the in vitro to in vivo transition. Ranking models according to relative transcript expression in vivo has the potential to improve initial model selection. For example, combining p53 tumor expression data with mutational status could guide selection of tumors for therapeutic studies of agents where p53 status purportedly affects efficacy (e.g., MK-1775). The utility of monitoring changes in gene expression with extended in vivo tumor passages was illustrated by focused studies of drug resistance mediators and receptor tyrosine kinases. Noteworthy observations included a significant decline in HCT-15 colon xenograft ABCB1 transporter expression and increased expression of the kinase KIT in A549 with serial passage. These trends predict sensitivity to agents such as paclitaxel (ABCB1 substrate) and imatinib (c-KIT inhibitor) would be altered with extended passage. Given that gene expression results indicated some models undergo profound changes with in vivo passage, a general metric of stability was generated so models could be ranked accordingly. Lastly, changes occurring during transition from in vitro to in vivo growth may have important consequences for therapeutic studies since targets identified in vitro could be over- or under-represented when tumor cells adapt to in vivo growth. A comprehensive list of mouse transcripts capable of cross-hybridizing with human probe sets on the HG-U133 Plus 2.0 array was generated. Removal of the murine artifacts followed by pairwise analysis of in vitro cells with respective passage 1 xenografts and GO analysis illustrates the complex interplay that each model has with the host microenvironment.ConclusionsThis study provides strategies to aid selection of xenograft models for therapeutic studies. These data highlight the dynamic nature of xenograft models and emphasize the importance of maintaining passage consistency throughout experiments.Electronic supplementary materialThe online version of this article (doi: 10.1186/1471-2164-15-393) contains supplementary material, which is available to authorized users.

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Microsomal glutathione transferase 1 in anticancer drug resistance

Cited by 50 publications

References 32 publications

Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters

Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters

Clinical utility of glutathione-S-transferases, Alkaline Phosphatase and Lactate Dehydrogenase activity in oesophagus cancer patients before and after chemotherapy for Diagnosis and Prognosis

Gene expression profiling of 49 human tumor xenografts from in vitro culture through multiple in vivo passages - strategies for data mining in support of therapeutic studies

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