Abstract:
:The glutamine transporter ASCT2 (SLC1A5) is actively investigated as an oncological target, but the field lacks efficient ASCT2 inhibitors. A new group of ASCT2 inhibitors, 2-amino-4-bis(aryloxybenzyl)aminobutanoic acids (AABA), were developed recently and shown to suppress tumor growth in preclinical in vivo models. To test its specificity, we deleted ASCT2 in two human cancer cell lines. Surprisingly, growth of parental and ASCT2-knockout cells was equally sensitive to AABA compounds. AABA compounds inhibited glutamine transport in cells lacking ASCT2, but not in parental cells. Deletion of ASCT2 and amino acid (AA) depletion induced expression of SNAT2 (SLC38A2), the activity of which was inhibited by AABA compounds. They also potently inhibited isoleucine uptake via LAT1 (SLC7A5), a transporter that is upregulated in cancer cells together with ASCT2. Inhibition of SNAT2 and LAT1 was confirmed by recombinant expression in Xenopus laevis oocytes. The reported reduction of tumor growth in pre-clinical models may be explained by a significant disruption of AA homeostasis.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Bröer A,Fairweather S,Bröer Sdoi
10.3389/fphar.2018.00785subject
Has Abstractpub_date
2018-07-19 00:00:00pages
785issn
1663-9812journal_volume
9pub_type
杂志文章abstract::Adult-onset Still's disease (AOSD) is a rare inflammatory disease of unknown etiology typically characterized by episodes of spiking fever, evanescent rash, arthralgia, leukocytosis, and hyperferritinemia. The pivotal role of interleukin (IL)-1 and other pro-inflammatory cytokines gives rise to the development of new ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01074
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pub_type: 杂志文章,评审
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00429
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abstract::Endothelium dysfunction induced by reactive oxygen species (ROS) is an important initial event at the onset of myocardial ischemia/reperfusion in which the Egr-1 transcription factor often serves as a master switch for various damage pathways following reperfusion injury. We hypothesized that an intracellular ROS/MAPK...
journal_title:Frontiers in pharmacology
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abstract::The exponential growth of the Internet of Things and the global popularity and remarkable decline in cost of the mobile phone is driving the digital transformation of medical practice. The rapidly maturing digital, non-medical world of mobile (wireless) devices, cloud computing and social networking is coalescing with...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
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abstract::Hypertensive disorders of pregnancy (HDP) are a group of morbid pregnancy complications, with preeclampsia (PE) being the most common subclassification among them. PE affects 2%-8% of pregnancies globally and threatens maternal and fetal health seriously. However, the only effective treatment of PE to date is the time...
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2012.00043
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abstract:BACKGROUND:Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00123
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
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abstract::Flavonoids are some of the most important natural products with a variety of physiological activities. 8-Formylophiopogonanone B (8-FOB) is a naturally existing homoisoflavonoid in Ophiopogon japonicus. Paraquat (PQ) has been widely used as a potent herbicide and has high toxicity in humans. The goal of the present st...
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doi:10.3389/fphar.2019.01525
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abstract:Background:Depression is a long-term complex psychiatric disorder, and its etiology remains largely unknown. Valeriana jatamansi Jones ex Roxb (V. jatamansi) is used in the clinic for the treatment of depression, but there are insufficient reports of its antidepressive mechanisms and a poor understanding of its endogen...
journal_title:Frontiers in pharmacology
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doi:10.3389/fphar.2020.00338
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abstract::Stability of traditional Chinese medicine injection (TCMI) is an important issue related with its clinical application. TCMI is composed of multi-components, therefore, when evaluating TCMI stability, several marker compounds cannot represent global components or biological activities of TCMI. Till now, when evaluatin...
journal_title:Frontiers in pharmacology
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doi:10.3389/fphar.2017.00833
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2013.00154
更新日期:2013-12-12 00:00:00
abstract::[This retracts the article on p. 15 in vol. 2, PMID: 21687510.]. ...
journal_title:Frontiers in pharmacology
pub_type: 撤回出版物
doi:10.3389/fphar.2014.00283
更新日期:2014-12-17 00:00:00
abstract::It is currently thought that the dementia of Alzheimer's disease is due to the neurotoxicity of the deposits or aggregates of amyloid-β (Aβ) in the extracellular space of the cerebral cortex. This model has been widely criticized because there is a poor correlation between deposits and dementia. Others have questioned...
journal_title:Frontiers in pharmacology
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doi:10.3389/fphar.2013.00059
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abstract::Salmonella typhimurium is a highly transmissible pathogen in rabbits that causes significant losses. Danofloxacin shows excellent efficacy against S. typhimurium infections. However, there are few reports of the pharmacokinetic/pharmacodynamic (PK/PD) modeling of danofloxacin against this pathogen. The aim of this stu...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00391
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journal_title:Frontiers in pharmacology
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abstract::This study investigated the role of miR-3188 on the proliferation of non-small cell lung cancer cells and its relationship to FOXO1-modulated feedback loop. Two non-small cell lung cancer (NSCLC) cell lines A549 and H1299 were used. RNA silencing was achieved by lentiviral transfection. Cell proliferation was assessed...
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pub_type: 杂志文章
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journal_title:Frontiers in pharmacology
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pub_type: 杂志文章
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