Glyoxalases in Urological Malignancies

Antognelli, Cinzia; Talesa, Vincenzo Nicola

doi:10.3390/ijms19020415

Cited by 50 publications

(77 citation statements)

References 131 publications

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“…Particularly, MG is known as a highly toxic and reactive carbonyl compound that spontaneously glycates proteins, nucleic acids, and lipids [19]. MG detoxification is accomplished mainly by glyoxalase-1, and both high expression and activity of this enzyme have been demonstrated in PCa, BC, and RC [20], explaining the decrease in MG urinary levels in all urological cancers compared to controls.…”

Section: Discussionmentioning

confidence: 99%

A Panel of Urinary Volatile Biomarkers for Differential Diagnosis of Prostate Cancer from Other Urological Cancers

Lima

Pinto

Carvalho‐Maia

et al. 2020

Cancers

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Our group recently developed a urinary 6-biomarker panel for the diagnosis of prostate cancer (PCa) which has a higher level of accuracy compared to the serum prostate specific antigen (PSA) test. Herein, urine from an independent cohort of PCa patients and cancer-free controls was analyzed to further validate the discriminative power of that panel. Additionally, urine from patients diagnosed with bladder cancer (BC) and renal cancer (RC) were included to evaluate the site-specificity of the panel. Results confirmed the ability of the 6-biomarker panel to discriminate PCa patients from controls, but not from other urological cancers. To overcome this limitation, an untargeted approach was performed to unveil discriminant metabolites among the three cancer types. A 10-biomarker panel comprising the original panel plus four new metabolites was established to discriminate PCa from controls, BC, and RC, with 76% sensitivity, 90% specificity, and 92% accuracy. This improved panel also disclosed better accuracy than serum PSA test and provides the basis for a new non-invasive early detection tool for PCa.

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Section: Discussionmentioning

confidence: 99%

A Panel of Urinary Volatile Biomarkers for Differential Diagnosis of Prostate Cancer from Other Urological Cancers

Lima

Pinto

Carvalho‐Maia

et al. 2020

Cancers

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“…This phenomenon was, first, described in 1920 by Otto Warburg and is called the "Warburg effect" [29,30]. Alternatively, enhanced glycolysis may likely result in accumulation of the methylglyoxal (MG) cytotoxic metabolite that is spontaneously formed by the degradation of two glycolytic intermediates [31]. Hence, cancer cells, in order to avoid MG-induced self-destruction, and as a survival strategy, upregulate the glyoxalase-dependent enzymatic machinery to remove MG and convert it into D-lactic acid, thus causing its cellular accumulation [31].…”

Section: Discussionmentioning

confidence: 99%

Human Melanoma-Cell Metabolic Profiling: Identification of Novel Biomarkers Indicating Metastasis

Kosmopoulou

Giannopoulou

Iliou

et al. 2020

IJMS

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Melanoma is the most aggressive type of skin cancer, leading to metabolic rewiring and enhancement of metastatic transformation. Efforts to improve its early and accurate diagnosis are largely based on preclinical models and especially cell lines. Hence, we herein present a combinational Nuclear Magnetic Resonance (NMR)- and Ultra High Performance Liquid Chromatography-High-Resolution Tandem Mass Spectrometry (UHPLC-HRMS/MS)-mediated untargeted metabolomic profiling of melanoma cells, to landscape metabolic alterations likely controlling metastasis. The cell lines WM115 and WM2664, which belong to the same patient, were examined, with WM115 being derived from a primary, pre-metastatic, tumor and WM2664 clonally expanded from lymph-node metastases. Metabolite samples were analyzed using NMR and UHPLC-HRMS. Multivariate statistical analysis of high resolution NMR and MS (positive and negative ionization) results was performed by Principal Component Analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA) and Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA), while metastasis-related biomarkers were determined on the basis of VIP lists, S-plots and Student’s t-tests. Receiver Operating Characteristic (ROC) curves of NMR and MS data revealed significantly differentiated metabolite profiles for each cell line, with WM115 being mainly characterized by upregulated levels of phosphocholine, choline, guanosine and inosine. Interestingly, WM2664 showed notably increased contents of hypoxanthine, myo-inositol, glutamic acid, organic acids, purines, pyrimidines, AMP, ADP, ATP and UDP(s), thus indicating the critical roles of purine, pyrimidine and amino acid metabolism during human melanoma metastasis.

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“…Therefore, via the glyoxalase pathway, the cellular detoxification of the reactive dicarbonyl metabolite, MG is essentially implemented [16,17]. In this pathway, Glo-1, a major MG detoxifying enzyme, catalyzes the first and the rate-limiting step in the removal of MG, and is crucial in protecting cells against oxidative stress [18,19]. A lack of Glo-1 elicits damage to mitochondria due to increased ROS production [20].…”

Section: Discussionmentioning

confidence: 99%

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

Yoo

Hong

et al. 2020

Antioxidants

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To investigate the anti-diabetic properties of chebulic acid (CA) associated with the prevention of methyl glyoxal (MG)-induced mitochondrial dysfunction in INS-1 pancreatic β-cells, INS-1 cells were pre-treated with CA (0.5, 1.0, and 2.0 μM) for 48 h and then treated with 2 mM MG for 8 h. The effects of CA and MG on INS-1 cells were evaluated using the following: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; glyoxalase 1 (Glo-1) expression via Western blot and enzyme activity assays; Nrf-2, nuclear factor erythroid 2-related factor 2 protein expression via Western blot assay; reactive oxygen species (ROS) production assay; mRNA expression of mitochondrial dysfunction related components (UCP2, uncoupling protein 2; VDAC1, voltage-dependent anion-selective channel-1; cyt c, cytochrome c via quantitative reverse transcriptase-PCR; mitochondrial membrane potential (MMP); adenosine triphosphate (ATP) synthesis; glucose-stimulated insulin secretion (GSIS) assay. The viability of INS-1 cells was maintained upon pre-treating with CA before exposure to MG. CA upregulated Glo-1 protein expression and enzyme activity in INS-1 cells and prevented MG-induced ROS production. Mitochondrial dysfunction was alleviated by CA pretreatment; this occurred via the downregulation of UCP2, VDAC1, and cyt c mRNA expression and the increase of MMP and ATP synthesis. Further, CA pre-treatment promoted the recovery from MG-induced decrease in GSIS. These results indicated that CA could be employed as a therapeutic agent in diabetes due to its ability to prevent MG-induced development of insulin sensitivity and oxidative stress-induced dysfunction of β-cells.

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Glyoxalases in Urological Malignancies

Cited by 50 publications

References 131 publications

A Panel of Urinary Volatile Biomarkers for Differential Diagnosis of Prostate Cancer from Other Urological Cancers

A Panel of Urinary Volatile Biomarkers for Differential Diagnosis of Prostate Cancer from Other Urological Cancers

Human Melanoma-Cell Metabolic Profiling: Identification of Novel Biomarkers Indicating Metastasis

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

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