scholarly journals Metabolic Rewiring and the Characterization of Oncometabolites

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2900
Author(s):  
Diren Beyoğlu ◽  
Jeffrey R. Idle
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Metabolic Phenotype ◽  
Low Molecular Weight ◽  
Histone Demethylases ◽  
Epigenetic Landscape ◽  
Enzyme Promiscuity ◽  
High Concentrations ◽  
Definition Of

The study of low-molecular-weight metabolites that exist in cells and organisms is known as metabolomics and is often conducted using mass spectrometry laboratory platforms. Definition of oncometabolites in the context of the metabolic phenotype of cancer cells has been accomplished through metabolomics. Oncometabolites result from mutations in cancer cell genes or from hypoxia-driven enzyme promiscuity. As a result, normal metabolites accumulate in cancer cells to unusually high concentrations or, alternatively, unusual metabolites are produced. The typical oncometabolites fumarate, succinate, (2R)-hydroxyglutarate and (2S)-hydroxyglutarate inhibit 2-oxoglutarate-dependent dioxygenases, such as histone demethylases and HIF prolyl-4-hydroxylases, together with DNA cytosine demethylases. As a result of the cancer cell acquiring this new metabolic phenotype, major changes in gene transcription occur and the modification of the epigenetic landscape of the cell promotes proliferation and progression of cancers. Stabilization of HIF1α through inhibition of HIF prolyl-4-hydroxylases by oncometabolites such as fumarate and succinate leads to a pseudohypoxic state that promotes inflammation, angiogenesis and metastasis. Metabolomics has additionally been employed to define the metabolic phenotype of cancer cells and patient biofluids in the search for cancer biomarkers. These efforts have led to the uncovering of the putative oncometabolites sarcosine, glycine, lactate, kynurenine, methylglyoxal, hypotaurine and (2R,3S)-dihydroxybutanoate, for which further research is required.

scholarly journals Characterization of Liposomes for Cancer Cell Transfection

2007 ◽  
Vol 1 (1) ◽  
pp. 60-63
Author(s):  
Svetlana A Tatarkova ◽  
Satvinder Khaira
Keyword(s):  
Surface Charge ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Surface Potential ◽  
Cell Transfection ◽  
Similar Extent ◽  
Positive Surface Charge ◽  
Negative Surface ◽  
Subsequent Addition

We have characterized a broad range of liposome formulations with varying DcChol:DOPE ratio. Subsequent addition of DcChol to liposomes increases its positive surface charge. However, loading the nuclear acids did not neutralize the overall negative surface potential to a similar extent. The liposomes were tested by transfection of DNA in living cancer cells.

scholarly journals Electrical Impedance Spectroscopy for Monitoring Chemoresistance of Cancer Cells

Micromachines ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 832
Author(s):  
Lexi Crowell ◽  
Juan Yakisich ◽  
Brian Aufderheide ◽  
Tayloria Adams
Keyword(s):  
Impedance Spectroscopy ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cellular Response ◽  
Electrical Impedance ◽  
Electrical Impedance Spectroscopy ◽  
Cell Behavior ◽  
Drug Resistant ◽  
Cancerous Cells

Electrical impedance spectroscopy (EIS) is an electrokinetic method that allows for the characterization of intrinsic dielectric properties of cells. EIS has emerged in the last decade as a promising method for the characterization of cancerous cells, providing information on inductance, capacitance, and impedance of cells. The individual cell behavior can be quantified using its characteristic phase angle, amplitude, and frequency measurements obtained by fitting the input frequency-dependent cellular response to a resistor–capacitor circuit model. These electrical properties will provide important information about unique biomarkers related to the behavior of these cancerous cells, especially monitoring their chemoresistivity and sensitivity to chemotherapeutics. There are currently few methods to assess drug resistant cancer cells, and therefore it is difficult to identify and eliminate drug-resistant cancer cells found in static and metastatic tumors. Establishing techniques for the real-time monitoring of changes in cancer cell phenotypes is, therefore, important for understanding cancer cell dynamics and their plastic properties. EIS can be used to monitor these changes. In this review, we will cover the theory behind EIS, other impedance techniques, and how EIS can be used to monitor cell behavior and phenotype changes within cancerous cells.

scholarly journals Pentagalloylglucose, isolated from the leaf extract of Anacardium occidentale L., could elicit rapid and selective cytotoxicity in cancer cells

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Bamigboye J. Taiwo ◽  
Temidayo D. Popoola ◽  
Fanie R. van Heerden ◽  
Amos A. Fatokun
Keyword(s):  
Oxidative Stress ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Leaf Extract ◽  
Anacardium Occidentale ◽  
Selective Cytotoxicity ◽  
Anti Oxidant ◽  
High Concentrations ◽  
Foetal Lung

ABSTRACT Background The leaf of Anacardium occidentale L. has been a component of many herbal recipes in South-Western Nigeria. The work reported herein, therefore, explored the phytochemical composition of this plant and the potential anti-cancer activity of an isolated chemical constituent. Methods Phytochemical methods (including chromatographic analysis) combined with spectroscopic and spectrometric analyses (IR, HRMS and NMR (1D and 2D)) were used to identify chemical constituents. Cytotoxic effects were determined using the MTT viability assay and bright-field imaging. Induction of oxidative stress was determined using the fluorescence-based 2′,7′-dichlorofluorescein diacetate (DCFDA) assay. Results For the first time in the plant, Compound 1 was isolated from the leaf extract and identified as pentagalloylglucose. Compound 1 was significantly cytotoxic against the cancer cell lines HeLa (human cervical adenocarcinoma cell line) and MRC5-SV2 (human foetal lung cancer cell line), with IC50 of 71.45 and 52.24 μg/ml, respectively. The selectivity index (SI) for Compound 1 was 1.61 (IC50 against the normal human foetal lung fibroblast cell line MRC-5 was 84.33μg/ml), demonstrating better cancer cell-selectivity compared to doxorubicin with a SI of 1.28. The cytotoxic activity of Compound 1 in HeLa cells was also rapid, as shown by its concentration- and time-dependent 3 h and 6 h cytotoxicity profiles, an effect not observed with doxorubicin. Generation of reactive oxygen species at high concentrations of pentagalloylglucose to induce oxidative stress in cancer cells was identified as a mechanistic event that led to or resulted from its cytotoxicity. Conclusions We suggest that pentagalloylglucose is selectively cytotoxic to cancer cells, and at high concentrations could exhibit pro-oxidant effects in those cells, as opposed to its general anti-oxidant effects in cells. Also, the presence of Compound 1 (pentagalloylglucose) in the plant and its cancer cell-selective cytotoxicity provide some rationale for the ethno-medicinal use of the plant’s leaf extract for treating diseases associated with excessive cell proliferation. Further studies are required to dissect the molecular mechanisms and players differentially regulating the biphasic anti-oxidant and pro-oxidant effects of pentagalloylglucose in normal and cancer cells.

scholarly journals Physical and Biological Evaluation of Low-Molecular-Weight Hyaluronic Acid/Fe3O4 Nanoparticle for Targeting MCF7 Breast Cancer Cells

Polymers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1094 ◽  
Author(s):  
Hsin-Ta Wang ◽  
Po-Chien Chou ◽  
Ping-Han Wu ◽  
Chi-Ming Lee ◽  
Kang-Hsin Fan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Weight ◽  
Hyaluronic Acid ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Low Molecular Weight ◽  
Cell Targeting ◽  
Fe3o4 Nps ◽  
Targeting Ability

Low-molecular-weight hyaluronic acid (LMWHA) was integrated with superparamagnetic Fe3O4 nanoparticles (Fe3O4 NPs). The size distribution, zeta potential, viscosity, thermogravimetric and paramagnetic properties of the LMWHA-Fe3O4 NPs were systematically examined. For cellular experiments, MCF7 breast cancer cell line was carried out. In addition, the cell targeting ability and characteristics of the LMWHA-Fe3O4 NPs for MCF7 breast cancer cells were analyzed using the thiocyanate method and time-of-flight secondary ion mass spectrometry (TOF-SIMS). The experimental results showed that the LMWHA-Fe3O4 NPs were not only easily injectable due to their low viscosity, but also exhibited a significant superparamagnetic property. Furthermore, the in vitro assay results showed that the NPs had negligible cytotoxicity and exhibited a good cancer cell targeting ability. Overall, the results therefore suggest that the LMWHA-Fe3O4 NPs have considerable potential as an injectable agent for enhanced magnetic resonance imaging (MRI) and/or hyperthermia treatment in breast cancer therapy.

scholarly journals Cytotoxic Effects of Coated Gold Nanoparticles on PC12 Cancer Cell

2018 ◽  
Vol 7 ◽  
pp. e1110
Author(s):  
Hadi Zare Marzouni ◽  
Fazel Tarkhan ◽  
Amir Aidun ◽  
Kiana Shahzamani ◽  
Hamid Reza Jahan Tigh ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Amino Acid ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Oxygen Species ◽  
Cytotoxic Effects ◽  
Coated Nanoparticles ◽  
Cellular Life ◽  
Cellular Reactive Oxygen Species ◽  
High Concentrations

Background: The use of gold nanoparticles in medicine and especially in cancer treatment has been of interest to researchers. The effectiveness of this nanoparticle on cells significantly depends on the amount of its entry into the cells. This study was performed to compare the rate and mechanism of effect of gold nanoparticles coated with different amino acid on PC12 cancer cell line.Materials and Methods: The PC12 cells line were exposed to various concentrations of amino acid coated and uncoated gold nanoparticles (0.5, 2.5 and 5 μM). Cell death rate was determined according to level of Lactate dehydrogenase (LDH) release from cells and MTT assay. In addition cell morphology and the amount of Cellular Reactive oxygen species (ROS) were studied.Results: The uncoated gold nanoparticles have shown minor effects on cellular life. Gold nanoparticles coated by tryptophan at high concentrations (2.5, 5 and 25μM) increase in cancer cells metabolic activity. Gold nanoparticles coated by Aspartate also produce the largest amount of LDH and ROS in cancer cells and therefore caused of highest rate of apoptosis.Conclusion: The results showed that the nanoparticles coated with amino acids are affected on cellular metabolism and apoptosis more than uncoated nanoparticles. Also the smallest coated nanoparticles (coated by aspartate) have the most influence and by increasing the size, this effect was reduced. [GMJ.2018;7:e1110]

scholarly journals Differential Effects of Gonadotropin-Releasing Hormone (GnRH)-I and GnRH-II on Prostate Cancer Cell Signaling and Death

2005 ◽  
Vol 90 (7) ◽  
pp. 4287-4298 ◽  
Author(s):  
Kaushik Maiti ◽  
Da Young Oh ◽  
Jung Sun Moon ◽  
Sujata Acharjee ◽  
Jian Hua Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Prostate Cancer Cells ◽  
Differential Effects ◽  
Cancer Cell Death ◽  
Therapeutic Drugs ◽  
High Concentrations ◽  
Cancer Cell Signaling

Abstract Context: GnRH is known to directly regulate prostate cancer cell proliferation, but the precise mechanism of action of the peptide is still under investigation. Objective: This study demonstrates differential effects of GnRH-I and GnRH-II on androgen-independent human prostate cancer cells. Results: Both GnRH-I and GnRH-II increased the intracellular Ca2+ concentration ([Ca2+]i) either through Ca2+ influx from external Ca2+ source or via mobilization of Ca2+ from internal Ca2+ stores. Interestingly, the [Ca2+]i increase was mediated by activation of the ryanodine receptor but not the inositol trisphosphate receptor. Trptorelix-1, a novel GnRH-II antagonist but not cetrorelix, a classical GnRH-I antagonist, completely inhibited the GnRH-II-induced [Ca2+]i increase. Concurrently at high concentrations, trptorelix-1 and cetrorelix inhibited GnRH-I-induced [Ca2+]i increase, whereas at low concentrations they exerted an agonistic action, inducing Ca2+ influx. High concentrations of trptorelix-1 but not cetrorelix-induced prostate cancer cell death, probably through an apoptotic process. Using photoaffinity labeling with 125I-[azidobenzoyl-d-Lys6]GnRH-II, we observed that an 80-kDa protein specifically bound to GnRH-II. Conclusions: This study suggests the existence of a novel GnRH-II binding protein, in addition to a conventional GnRH-I receptor, in prostate cancer cells. These data may facilitate the development of innovatory therapeutic drugs for the treatment of prostate cancer.

Feline urine metabolomic signature: characterization of low-molecular-weight substances in urine from domestic cats

2017 ◽  
Vol 20 (2) ◽  
pp. 155-163 ◽  
Author(s):  
Sol-Maiam Rivera-Vélez ◽  
Nicolas F Villarino
Keyword(s):  
Molecular Weight ◽  
Metabolic Pathways ◽  
Metabolic Phenotype ◽  
Low Molecular Weight ◽  
Domestic Cats ◽  
Ultrasound Guided ◽  
Relevant Role ◽  
Mass Spectrometery ◽  
Urine Metabolome

Objectives This aim of this study was to characterize the composition and content of the feline urine metabolome. Methods Eight healthy domestic cats were acclimated at least 10 days before starting the study. Urine samples (~2 ml) were collected by ultrasound-guided cystocentesis. Samples were centrifuged at 1000 × g for 8 mins, and the supernatant was analyzed by gas chromatography/time-of-flight mass spectrometery. The urine metabolome was characterized using an untargeted metabolomics approach. Results Three hundred and eighteen metabolites were detected in the urine of the eight cats. These molecules are key components of at least 100 metabolic pathways. Feline urine appears to be dominated by carbohydrates, carbohydrate conjugates, organic acid and derivatives, and amino acids and analogs. The five most abundant molecules were phenaceturic acid, hippuric acid, pseudouridine phosphate and 3-(4-hydroxyphenyl) propionic acid. Conclusions and relevance This study is the first to characterize the feline urine metabolome. The results of this study revealed the presence of multiple low-molecular-weight substances that were not known to be present in feline urine. As expected, the origin of the metabolites detected in urine was diverse, including endogenous compounds and molecules biosynthesized by microbes. Also, the diet seemed to have had a relevant role on the urine metabolome. Further exploration of the urine metabolic phenotype will open a window for discovering unknown, or poorly understood, metabolic pathways. In turn, this will advance our understanding of feline biology and lead to new insights in feline physiology, nutrition and medicine.

scholarly journals Melatonin Reprograms Glucose Metabolism in Cancer Cell Mitochondria

2019 ◽  
Vol 1 (3) ◽  
pp. 52-61
Author(s):  
Russel J. Reiter ◽  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Pyruvate Dehydrogenase Complex ◽  
Cancer Growth ◽  
Cell Phenotype ◽  
Acetyl Coa ◽  
History Of ◽  
Cancer Phenotype ◽  
High Concentrations ◽  
The Warburg Effect

Melatonin has a long history of studies which confirm its ability to inhibit cancer growth. Melatonin is present in high concentrations in the mitochondria of normal cells but is likely absent from the mitochondria of cancer cells, at least when isolated from tumors harvested during the day. Herein, we hypothesize that melatonin’s absence from cancer cell mitochondria prevents these organelles from metabolizing pyruvate to acetyl coenzyme A (acetyl-CoA) due to suppression of the activity of the enzyme pyruvate dehydrogenase complex (PDC), the enzyme that catalyzes the conversion of pyruvate to acetyl-CoA. This causes cancer cells to metabolize glucose to lactate in the cytosol (the Warburg effect). Since cancer cell mitochondria can take up nighttime pineal-derived melatonin from the blood, the indoleamine predictably promotes the conversion of pyruvate to acetyl-CoA in the mitochondria during the night. Thus, while cancer cells exhibit a typical cancer phenotype during the day, at night cancer cells have a more normal cell phenotype. Via similar actions, melatonin probably overcomes the insensitivity of cancers to chemotherapies. Hopefully, the hypothetical processes proposed herein will soon be experimentally tested.

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