Selective apoptosis-inducing activity of synthetic hydrocarbon-stapled SOS1 helix with d-amino acids in H358 cancer cells expressing KRASG12C

2020 ◽  
Vol 185 ◽  
pp. 111844 ◽  
Author(s):  
Li-li Xu ◽  
Cui-cui Li ◽  
Lu-yan An ◽  
Zhen Dai ◽  
Xiao-yi Chen ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benedikt Feuerecker ◽  
Philipp Biechl ◽  
Christof Seidl ◽  
Frank Bruchertseifer ◽  
Alfred Morgenstern ◽  
...  

AbstractEvaluation of treatment response is among the major challenges in modern oncology. We herein used a monoclonal antibody targeting the EGF receptor (EGFR) labelled with the alpha emitter 213Bi (213Bi-anti-EGFR-MAb). EJ28Luc (bladder) and LN18 (glioma) cancer cells, both overexpressing EGFR, were incubated for 3 h with the radioimmunoconjugate. To assess the responses in the core carbon metabolism upon this treatment, these cancer cell lines were subsequently cultivated for 18 h in the presence of [U-13C6]glucose. 13C-enrichment and isotopologue profiles of key amino acids were monitored by gas chromatography–mass spectrometry (GC/MS), in order to monitor the impacts of the radionuclide-treatment upon glucose metabolism. In comparison to untreated controls, treatment of EJ28Luc cells with 213Bi-anti-EGFR-MAb resulted in a significantly decreased incorporation of 13C from [U-13C6]glucose into alanine, aspartate, glutamate, glycine, proline and serine. In sharp contrast, the same amino acids did not display less 13C-enrichments during treatment of the LN18 cells. The data indicate early treatment response of the bladder cancer cells, but not of the glioma cells though cell lines were killed following 213Bi-anti-EGFR-MAb treatment. The pilot study shows that the 13C-labelling approach is a valid tool to assess the responsiveness of cancer cells upon radionuclide-treatment in considerable metabolic detail.


2014 ◽  
Vol 32 (1) ◽  
pp. 332-340 ◽  
Author(s):  
GANG WANG ◽  
LEI DAI ◽  
LAISHENG LUO ◽  
WEN XU ◽  
CHENJING ZHANG ◽  
...  

2009 ◽  
Vol 19 (16) ◽  
pp. 4814-4817 ◽  
Author(s):  
Malgorzata Drag-Zalesinska ◽  
Julita Kulbacka ◽  
Jolanta Saczko ◽  
Teresa Wysocka ◽  
Maciej Zabel ◽  
...  

2019 ◽  
Vol 122 (2) ◽  
pp. 150-156 ◽  
Author(s):  
Lisa Vettore ◽  
Rebecca L. Westbrook ◽  
Daniel A. Tennant

AbstractAn abundant supply of amino acids is important for cancers to sustain their proliferative drive. Alongside their direct role as substrates for protein synthesis, they can have roles in energy generation, driving the synthesis of nucleosides and maintenance of cellular redox homoeostasis. As cancer cells exist within a complex and often nutrient-poor microenvironment, they sometimes exist as part of a metabolic community, forming relationships that can be both symbiotic and parasitic. Indeed, this is particularly evident in cancers that are auxotrophic for particular amino acids. This review discusses the stromal/cancer cell relationship, by using examples to illustrate a number of different ways in which cancer cells can rely on and contribute to their microenvironment – both as a stable network and in response to therapy. In addition, it examines situations when amino acid synthesis is driven through metabolic coupling to other reactions, and synthesis is in excess of the cancer cell’s proliferative demand. Finally, it highlights the understudied area of non-proteinogenic amino acids in cancer metabolism and their potential role.


Talanta ◽  
2017 ◽  
Vol 162 ◽  
pp. 285-292 ◽  
Author(s):  
Xiaona Li ◽  
Chi Chun Wong ◽  
Zhi Tang ◽  
Jianlin Wu ◽  
Shangfu Li ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2028 ◽  
Author(s):  
Mariafrancesca Scalise ◽  
Lara Console ◽  
Filomena Rovella ◽  
Michele Galluccio ◽  
Lorena Pochini ◽  
...  

Cancer cells perform a metabolic rewiring to sustain an increased growth rate and compensate for the redox stress caused by augmented energy metabolism. The metabolic changes are not the same in all cancers. Some features, however, are considered hallmarks of this disease. As an example, all cancer cells rewire the amino acid metabolism for fulfilling both the energy demand and the changed signaling routes. In these altered conditions, some amino acids are more frequently used than others. In any case, the prerequisite for amino acid utilization is the presence of specific transporters in the cell membrane that can guarantee the absorption and the traffic of amino acids among tissues. Tumor cells preferentially use some of these transporters for satisfying their needs. The evidence for this phenomenon is the over-expression of selected transporters, associated with specific cancer types. The knowledge of the link between the over-expression and the metabolic rewiring is crucial for understanding the molecular mechanism of reprogramming in cancer cells. The continuous growth of information on structure–function relationships and the regulation of transporters will open novel perspectives in the fight against human cancers.


2020 ◽  
Vol 27 ◽  
Author(s):  
Petr Stepka ◽  
Vit Vsiansky ◽  
Martina Raudenska ◽  
Jaromir Gumulec ◽  
Vojtech Adam ◽  
...  

: Metabolic changes driven by the hostile tumor microenvironment surrounding cancer cells and effect of these changes on tumorigenesis and metastatic potential have been known for a long time. The usual point of interest is glucose and changes in its utilization by cancer cells, mainly in the form of the Warburg effect. However, amino acids, both intra- and extracellular, also represent an important aspect of tumour microenvironment, which can have a significant effect on cancer cell metabolism and overall development of the tumor. Namely alterations in metabolism of amino acids glutamine, sarcosine, aspartate, methionine and cysteine have been previously connected to the tumor progression and aggressivity of prostate cancer. The aim of this review is to pinpoint current gaps in our knowledge of the role of amino acids as a part of the tumor microenvironment and to show effect of various amino acids on cancer cell metabolism and metastatic potential. This review shows limitations and exceptions from the traditionally accepted model of Warburg effect in some cancer tissues, with the emphasis on prostate cancer, because the traditional definition of Warburg effect as a metabolic switch to aerobic glycolysis does not always apply. Prostatic tissue both in healthy and transformed state significantly differs in many metabolic aspects, including the metabolisms of glucose and amino acids, from metabolism of other tissues. Findings from different tissues are therefore not always interchangeable and have to be taken into account during experimentation modifying the environment of tumor tissue by amino acid supplementation or depletion, which could potentially serve as a new therapeutic approach.


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