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International Journal of Cancer Jun 2018One of the hallmarks of cancer cells is the increased ability to acquire nutrients, particularly glucose and glutamine. Proliferating cells need precursors for cell... (Review)
Review
One of the hallmarks of cancer cells is the increased ability to acquire nutrients, particularly glucose and glutamine. Proliferating cells need precursors for cell growth and NADPH reducing equivalents for survival. The principal responsible for glucose uptake is facilitative glucose transporters (GLUTs), which usually are overexpressed in cancer cells. Besides their role in glucose uptake, GLUT transporters are able to transport other compounds such as dehydroascorbic acid or uric acid. They play a major role in tumor progression and cellular processes such as regulated cell death. The prostate gland has the particular characteristic of being more glycolytic than other non-pathological tissues given an accumulation of citrate in the seminal fluid and the inhibition of m-aconitase that affects to tricarboxylic acid cycle. In prostate cancer (PCa), androgens increase glucose uptake, upregulate GLUT transporters such as GLUT1 and GLUT3 and stimulate AMP-activated protein kinase pathway, suggesting a possible connection between glycolytic and androgenic signaling. Interestingly, diabetes is not a risk factor for PCa, as it is in other cancers, while insulin stimulates progression and insulin-like growth factor 1 pathway plays an important role in PCa progression. It was recently found that PCa cells overexpress GLUT4 and, more importantly, that it seems to be related to the castration-resistant prostate cancer (CRPC) phenotype, although little is known about its participation in tumor progression. This review will focus on the role of GLUT transporters along with PCa progression, and the involvement of GLUT4 on CRPC phenotype transition would be considered.
Topics: Adenocarcinoma; Glucose Transport Proteins, Facilitative; Humans; Male; Prostatic Neoplasms
PubMed: 29159872
DOI: 10.1002/ijc.31165 -
Free Radical Biology & Medicine Sep 2019Ascorbic acid (vitamin C) plays a significant role in the prevention of oxidative stress. In this process, ascorbate is oxidized to dehydroascorbate (DHA). We have...
Ascorbic acid (vitamin C) plays a significant role in the prevention of oxidative stress. In this process, ascorbate is oxidized to dehydroascorbate (DHA). We have investigated the impact of DHA on peptide/protein intramolecular disulfide formation as well as S-glutathionylation and S-homocysteinylation. S-glutathionylation of peptides/proteins is a reversible, potential regulatory mechanism in oxidative stress. Although the exact role of protein S-homocysteinylation is unknown, it has been proposed to be of importance in pathobiological processes such as onset of cardiovascular disease. Using an in vitro model system, we demonstrate that DHA causes disulfide bond formation within the active site of recombinant human glutaredoxin (Grx-1). DHA also facilities the formation of S-glutathionylation and S-homocysteinylation of a model peptide (AcFHACAAK) as well as Grx-1. We discuss the possible mechanisms of peptide/protein S-thiolation, which can occur either via thiol exchange or a thiohemiketal intermediate. A thiohemiketal DHA-peptide adduct was detected by mass spectrometry and its location on the peptide/protein cysteinyl thiol group was unambiguously confirmed by tandem mass spectrometry. This demonstrates that peptide/protein S-thiolation mediated by DHA is not limited to thiol exchange reactions but also takes place directly via the formation of a thiohemiketal peptide intermediate. Finally, we investigated a potential reducing role of glutathione (GSH) in the presence of S-homocysteinylated peptide/protein adducts. S-homocysteinylated AcFHACAAK, human hemoglobin α-chain and Grx-1 were incubated with GSH. Both peptide and proteins were reduced, and homocysteine replaced with GS-adducts by thiol exchange, as a function of time.
Topics: Antioxidants; Catalytic Domain; Cysteine; Dehydroascorbic Acid; Dimerization; Disulfides; Glutaredoxins; Glutathione; Hemoglobins; Homocysteine; Humans; Oxidation-Reduction; Oxidative Stress; Peptides; Sulfhydryl Compounds
PubMed: 31228548
DOI: 10.1016/j.freeradbiomed.2019.06.022 -
Advances in Nutrition (Bethesda, Md.) Mar 2016Adequate plasma, cellular, and tissue vitamin C concentrations are required for maintaining optimal health through suppression of oxidative stress and optimizing... (Review)
Review
Adequate plasma, cellular, and tissue vitamin C concentrations are required for maintaining optimal health through suppression of oxidative stress and optimizing functions of certain enzymes that require vitamin C as a cofactor. Polymorphisms in the vitamin C transporter genes, compromising genes encoding sodium-dependent ascorbate transport proteins, and also genes encoding facilitative transporters of dehydroascorbic acid, are associated with plasma and tissue cellular ascorbate status and hence cellular redox balance. This review summarizes our current knowledge of the links between variations in vitamin C transporter genes and common chronic diseases. We conclude that emerging genetic knowledge has a good likelihood of defining future personalized dietary recommendations and interventions; however, further validations through biological studies as well as controlled dietary trials are required to identify predictive and actionable genetic biomarkers. We further advocate the need to consider genetic variation of vitamin C transporters in future clinical and epidemiologic studies on common complex diseases.
Topics: Chronic Disease; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Glucose Transport Proteins, Facilitative; Humans; Nutrigenomics; Oxidative Stress; Polymorphism, Single Nucleotide; Protein Isoforms; Sodium-Coupled Vitamin C Transporters
PubMed: 26980812
DOI: 10.3945/an.115.009225 -
Roczniki Panstwowego Zakladu Higieny 2021Vitamin C is one of the most important water-soluble vitamins. It is responsible for many important functions in the body, including: it has a positive effect on...
BACKGROUND
Vitamin C is one of the most important water-soluble vitamins. It is responsible for many important functions in the body, including: it has a positive effect on maintaining immunity, protects the body against free radicals, and also participates in the synthesis of hormones. Juices can be a good source of this vitamin. Most of the juices available on the market are processed products. Untreated juices, which do not contain added preservatives, sugar and are not pasteurized, constitute a smaller group on the market. Therefore, this group of juices can be a valuable product in human nutrition.
OBJECTIVE
The aim of the study was t o analyze the content of ascorbic acid (AA), dehydroascorbic acid (DHAA) and vitamin C (TAA) in non-preserved juices, depending on their type and storage time.
MATERIAL AND METHODS
The analysis of T AA, AA and DHAA content in juices was carried out in ten types of nonpreserved juices from two companies (A and B), purchased in a chain of retail outlets. The analyzed juices in company A were: sauerkraut and carrot, grapefruit, orange, apple and mandarin, while in company B: orange, apple, apple and quince, grapefruit and mandarin. In test 1, the first ten juices were analyzed, in test 2 - another ten juices after one month, in test 3 - juices from test 2 were used, and three days after opening the package and storing the juices in standard refrigeration conditions, the stability test of AA was analyzed. The AA and TAA contents were determined using the high performance liquid chromatography (HPLC) method. The DHAA content was calculated by subtracting the AA content from the TAA content.
RESULTS
The highest TAA content was found in citrus juices, i.e. grapefruit, orange and mandarin, and the lowest in sauerkraut and carrot juices and apple juice. Moreover, ascorbic acid in apple juice was characterized by the lowest durability.
CONCLUSIONS
In the production of non-preserved apple juice, consideration should be given to the natural protection of ascorbic acid by the addition of citrus or other fruit juice, vegetable juice or by using a mild technology in the production process.
Topics: Ascorbic Acid; Citrus; Fruit; Humans; Vitamins
PubMed: 34928113
DOI: 10.32394/rpzh.2021.0187 -
Toxins Apr 2023Aflatoxins (AFs) are toxic secondary metabolites produced by spp. and are found in food and feed as contaminants worldwide. Due to climate change, AFs occurrence is...
Aflatoxins (AFs) are toxic secondary metabolites produced by spp. and are found in food and feed as contaminants worldwide. Due to climate change, AFs occurrence is expected to increase also in western Europe. Therefore, to ensure food and feed safety, it is mandatory to develop green technologies for AFs reduction in contaminated matrices. With this regard, enzymatic degradation is an effective and environmentally friendly approach under mild operational conditions and with minor impact on the food and feed matrix. In this work, Ery4 laccase, acetosyringone, ascorbic acid, and dehydroascorbic acid were investigated in vitro, then applied in artificially contaminated corn for AFB reduction. AFB (0.1 µg/mL) was completely removed in vitro and reduced by 26% in corn. Several degradation products were detected in vitro by UHPLC-HRMS and likely corresponded to AFQ, epi-AFQ, AFB-diol, or AFBdialehyde, AFB, and AFM. Protein content was not altered by the enzymatic treatment, while slightly higher levels of lipid peroxidation and HO were detected. Although further studies are needed to improve AFB reduction and reduce the impact of this treatment in corn, the results of this study are promising and suggest that Ery4 laccase can be effectively applied for the reduction in AFB in corn.
Topics: Aflatoxin B1; Zea mays; Hydrogen Peroxide; Laccase; Aflatoxins
PubMed: 37235345
DOI: 10.3390/toxins15050310 -
Small (Weinheim An Der Bergstrasse,... Jan 2023The acquired resistance to Osimertinib (AZD9291) greatly limits the clinical benefit of patients with non-small cell lung cancer (NSCLC), whereas AZD9291-resistant...
The acquired resistance to Osimertinib (AZD9291) greatly limits the clinical benefit of patients with non-small cell lung cancer (NSCLC), whereas AZD9291-resistant NSCLCs are prone to metastasis. It's challenging to overcome AZD9291 resistance and suppress metastasis of NSCLC simultaneously. Here, a nanocatalytic sensitizer (VF/S/A@CaP) is proposed to deliver Vitamin c (Vc)-Fe(II), si-OTUB2, ASO-MALAT1, resulting in efficient inhibition of tumor growth and metastasis of NSCLC by synergizing with AHP-DRI-12, an anti-hematogenous metastasis inhibitor by blocking the amyloid precursor protein (APP)/death receptor 6 (DR6) interaction designed by our lab. Fe released from Vc-Fe(II) generates cytotoxic hydroxyl radicals (•OH) through Fenton reaction. Subsequently, glutathione peroxidase 4 (GPX4) is consumed to sensitize AZD9291-resistant NSCLCs with high mesenchymal state to ferroptosis due to the glutathione (GSH) depletion caused by Vc/dehydroascorbic acid (DHA) conversion. By screening NSCLC patients' samples, metastasis-related targets (OTUB2, LncRNA MALAT1) are confirmed. Accordingly, the dual-target knockdown plus AHP-DRI-12 significantly suppresses the metastasis of AZD9291-resistant NSCLC. Such modality leads to 91.39% tumor inhibition rate in patient-derived xenograft (PDX) models. Collectively, this study highlights the vulnerability to ferroptosis of AZD9291-resistant tumors and confirms the potential of this nanocatalytic-medicine-based modality to overcome critical AZD9291 resistance and inhibit metastasis of NSCLC simultaneously.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Ferroptosis; RNA, Long Noncoding; ErbB Receptors; Drug Resistance, Neoplasm; Ferrous Compounds; Cell Line, Tumor
PubMed: 36420659
DOI: 10.1002/smll.202204133 -
Foods (Basel, Switzerland) Dec 2022The citrus juice industry produces a large amount of fiber-rich waste and other bioactive compounds of great interest for their potential health benefits. This study...
The citrus juice industry produces a large amount of fiber-rich waste and other bioactive compounds of great interest for their potential health benefits. This study focuses on the valorization of the co-product resulting from the extraction of orange juice to offer it as a versatile, healthy, high-quality, and stable natural food ingredient in powder form. To this end, the vitamin C (VC) content (ascorbic and dehydroascorbic acid, AA and DHAA), major flavonoids (hesperidin and narirutin, HES and NAT), and techno-functional properties (angle of repose, AoR; hygroscopicity and wettability; density and porosity; mean particle size, MPS; water retention capacity, WRC; oil holding capacity, ORC; emulsifying and foaming capacity, EC and FC; and emulsion and foam stability, ES and FS) have been characterized. In addition, considering that dehydrated foods with high sugar content require the incorporation of high molecular weight biopolymers for their physical stabilization, the influence of starch modified with octenyl succinic acid (OSA) and gum Arabic (GA) on these properties has been studied. The results obtained confirm the high quality of this co-product to be offered as a powdered food ingredient with nutraceutical potential. The addition of the studied biopolymers is recommended as it does not modify the flowability of the powder and favors both the encapsulation of the bioactive compounds, especially in the presence of GA, and the rehydration capacity.
PubMed: 36613313
DOI: 10.3390/foods12010097 -
Biochemical and Biophysical Research... Sep 2016Due to its anti-obesity effects, an adipocyte-derived hormone, leptin, has become important for the treatment of obesity. However, most obese subjects are in a state of...
Due to its anti-obesity effects, an adipocyte-derived hormone, leptin, has become important for the treatment of obesity. However, most obese subjects are in a state of leptin resistance, and endoplasmic reticulum (ER) stress is suggested to be involved in the pathophysiology of leptin resistance. Dehydroascorbic acid (DHAA), an oxidized form of vitamin C, was found to be increased in diabetes. In the present study, we investigated the possible effects of DHAA on the activation of ER stress and leptin resistance. A human neuroblastoma cell line, stably transfected with the Ob-Rb leptin receptor (SH-SY5Y-ObRb), was treated with DHAA. We found that DHAA upregulated ER stress-related genes such as GRP78, CHOP, and spliced XBP1. Moreover, leptin-induced STAT3 phosphorylation was hindered by DHAA. These results suggested that increases in the levels of DHAA might be harmful to neurons, contributing to defective leptin-responsive signaling.
Topics: Cell Line, Tumor; Dehydroascorbic Acid; Endoplasmic Reticulum; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Gene Expression Regulation; Heat-Shock Proteins; Humans; Leptin; Neurons; Oxidation-Reduction; Phosphorylation; STAT3 Transcription Factor; Signal Transduction; Transcription Factor CHOP; Unfolded Protein Response; X-Box Binding Protein 1
PubMed: 27498033
DOI: 10.1016/j.bbrc.2016.08.013 -
Nutrients Dec 2020Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the... (Review)
Review
Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the activity of 2-oxoglutarate and Fe dependent dioxygenases (2-OGDD), which are involved in active DNA demethylation (TET proteins), the demethylation of histones, and hypoxia processes. Therefore, vitamin C may be engaged in the regulation of gene expression or in a hypoxic state. Hence, vitamin C has acquired great interest for its plausible effects on cancer treatment. Since its conceptualization, the role of vitamin C in cancer therapy has been a controversial and disputed issue. Vitamin C is transferred to the cells with sodium dependent transporters (SVCTs) and glucose transporters (GLUT). However, it is unknown whether the impaired function of these transporters may lead to carcinogenesis and tumor progression. Notably, previous studies have identified SVCTs' polymorphisms or their altered expression in some types of cancer. This review discusses the potential effects of vitamin C and the impaired SVCT function in cancers. The variations in vitamin C transporter genes may regulate the active transport of vitamin C, and therefore have an impact on cancer risk, but further studies are needed to thoroughly elucidate their involvement in cancer biology.
Topics: Ascorbic Acid; Basic Helix-Loop-Helix Transcription Factors; Brain Neoplasms; Breast Neoplasms; Carcinogenesis; DNA Methylation; DNA-Binding Proteins; Dehydroascorbic Acid; Dioxygenases; Epigenesis, Genetic; Female; Glioma; Glucose Transport Proteins, Facilitative; Hematologic Neoplasms; Homeostasis; Humans; Hypoxia-Inducible Factor 1; Ketoglutaric Acids; Male; Melanoma; Mixed Function Oxygenases; Neoplasms; Oxidation-Reduction; Polymorphism, Genetic; Prostatic Neoplasms; Proto-Oncogene Proteins; Sodium-Coupled Vitamin C Transporters; Vitamins
PubMed: 33352824
DOI: 10.3390/nu12123869 -
Nutrition and Cancer 2021Efforts to develop effective drugs targeting PI3K and KRAS signaling pathways in -mutant colorectal cancer stem cells (CRCSCs) remain challenging. Finding safe compounds...
The Safe Soluble Compound Dehydroascorbic Acid Inhibits Various Upstream and Downstream Effectors of PI3K and KRAS Signaling Pathways in Undruggable -Mutant Colorectal Cancer Stem-Like Cells.
Efforts to develop effective drugs targeting PI3K and KRAS signaling pathways in -mutant colorectal cancer stem cells (CRCSCs) remain challenging. Finding safe compounds that can easily enter CRCSCs with the ability to target metastasis-driver gene and pluripotency network genes as key upstream and downstream effectors of both PI3K and KRAS signaling pathways may provide promising results. -mutant CRCSCs display high expression of glucose transporters (GLUTs) on their cell membrane and a glycolytic phenotype providing an opportunity to deliver antiglycolytic compounds into these cells via the GLUTs. CRC patients with low levels of vitamin C in their plasma show a shorter survival suggesting the ability of this vitamin at the physiologic levels for caspase-3 activation and apoptosis in CRCSCs. Vitamin C in an oxidized form (L-dehydroascorbic acid; L-DHA) with antiglycolytic activity can be taken up into CRC cells via the GLUTs. This may provide selective toxicity on CRCSCs and affect and stemness markers genes expression in these cells. To this end, we treated /-mutant LS174T cells with high glycolytic activity as an attractive model for CRCSCs with L-DHA equal to the pharmacological levels of vitamin C in human plasma, after which cell numbers, metabolic activity, proliferation-rate, and pluripotency network genes expression, caspase-3 activity with apoptosis were evaluated. 48 h post-treatment with 100- to 1000 µM L-DHA, cell numbers were decreased and measured to be 70-47% control. L-DHA with selective toxicity on LS174T cells diminished metabolic activity and cell proliferation-rate to 1.4-0.8 (Control OD = 1.5) and 92-54.5% respectively with no toxicity on PBMCs. L-DHA decreased , , -2 and expression to 45%, 85%, 45% and 48% control respectively followed by caspase-3 reactivation by 2.5 to 4.9-fold increases and induction of apoptosis ranging from 0.5% to 58.3% for 100- to 1000 µM L-DHA. According to our data, CRC stem-like cells were highly sensitive to L-DHA in . L-DHA selectively targeted LS174T cells and successfully reactivated caspase-3 and apoptosis in these cells. , stemness marker genes and metabolic activity appear to be promising targets of L-DHA. Our results may provide a new therapeutic approach to target selectively GLUT-overexpressing -mutant CRCSCs using L-DHA with no toxicity on normal cells.
Topics: Cell Line, Tumor; Class I Phosphatidylinositol 3-Kinases; Colorectal Neoplasms; Dehydroascorbic Acid; Humans; Mutation; Neoplastic Stem Cells; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins p21(ras); Signal Transduction
PubMed: 33283545
DOI: 10.1080/01635581.2020.1856387