Hydrogen Sulfide Metabolism and Signaling in the Tumor Microenvironment

Giuffrè, Alessandro; Tomé, Catarina S.; Fernandes, Dalila G F; Zuhra, Karim; Vicente, João B.

doi:10.1007/978-3-030-34025-4_17

Cited by 39 publications

(26 citation statements)

References 127 publications

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“…Besides this, at physiological levels, H 2 S has different roles in a cell. It can function as a gaseous signaling molecule that freely diffuses across aqueous and hydrophobic biological boundaries, being the third “gasotransmitter” in mammalians’ physiology, as extensively reviewed by Giuffré et al [ 97 ]. Studies have shown that lower levels of H 2 S can act as an endogenous neuromodulator, inducing calcium release [ 98 ], and protect neurons from oxidative stress [ 99 ]; act as a smooth muscle relaxant [ 100 ] or as a vasodilator [ 101 ], as well as playing different roles in the inflammatory process [ 102 ].…”

Section: Cat Role In Physiology and In Cancermentioning

confidence: 99%

“…At low intracellular concentrations (0.01 to 1 μM), H 2 S may act as an electron donor to the mETC. H 2 S is oxidized by the membrane-attached mitochondrial sulfide:quinone oxidoreductase (SQR), which reduces coenzyme Q, while transferring a sulfane sulfur to an acceptor, such as sulfite or preferably GSH [ 97 , 103 ]. Reduced coenzyme Q is then reoxidized by complex III at the expense of cytochrome c reduction, which finally transfers electrons to cytochrome c oxidase to accomplish oxygen reduction [ 97 ], ultimately stimulating ATP production.…”

Section: Cat Role In Physiology and In Cancermentioning

confidence: 99%

“…H 2 S is oxidized by the membrane-attached mitochondrial sulfide:quinone oxidoreductase (SQR), which reduces coenzyme Q, while transferring a sulfane sulfur to an acceptor, such as sulfite or preferably GSH [ 97 , 103 ]. Reduced coenzyme Q is then reoxidized by complex III at the expense of cytochrome c reduction, which finally transfers electrons to cytochrome c oxidase to accomplish oxygen reduction [ 97 ], ultimately stimulating ATP production. However, at 3–30-fold higher concentrations, H 2 S reversibly inhibits cytochrome c oxidase with an inhibitory constant ( K i ) value of 0.2 μM at pH 7.4 [ 104 , 105 ] ( Figure 2 ), which underlines the double-faced nature of H 2 S in cellular bioenergetics.…”

Section: Cat Role In Physiology and In Cancermentioning

confidence: 99%

“…The exact role of CAT:MST in cancer development and progression remains under investigation, but several studies have focused on its final reaction product, H 2 S, and its role on cancer cells functioning. In fact, several cancer cell lines and tumor specimens have been shown to overexpress one or more of the H 2 S-synthesizing enzymes, including MST, resulting in increased H 2 S levels, which have been proposed to promote carcinogenesis through the regulation of various cancer-related processes [ 97 ]. In the last decade, a novel concept emerged in the field of cancer biology, demonstrating that various cancer cells can increase their endogenous H 2 S levels and use it in an autocrine and paracrine manner to promote cell proliferation, cytoprotective signaling, angiogenesis, and stimulate cellular bioenergetics [ 131 ].…”

Section: Role Of the Cat:mst Axis In Cancer Metabolic Remodelingmentioning

confidence: 99%

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Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer

Hipólito

Nunes

Vicente³

et al. 2020

Molecules

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Metabolic remodeling is a critical skill of malignant cells, allowing their survival and spread. The metabolic dynamics and adaptation capacity of cancer cells allow them to escape from damaging stimuli, including breakage or cross-links in DNA strands and increased reactive oxygen species (ROS) levels, promoting resistance to currently available therapies, such as alkylating or oxidative agents. Therefore, it is essential to understand how metabolic pathways and the corresponding enzymatic systems can impact on tumor behavior. Cysteine aminotransferase (CAT) per se, as well as a component of the CAT: 3-mercaptopyruvate sulfurtransferase (MST) axis, is pivotal for this metabolic rewiring, constituting a central mechanism in amino acid metabolism and fulfilling the metabolic needs of cancer cells, thereby supplying other different pathways. In this review, we explore the current state-of-art on CAT function and its role on cancer cell metabolic rewiring as MST partner, and its relevance in cancer cells’ fitness.

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Section: Cat Role In Physiology and In Cancermentioning

confidence: 99%

Section: Cat Role In Physiology and In Cancermentioning

confidence: 99%

Section: Cat Role In Physiology and In Cancermentioning

confidence: 99%

Section: Role Of the Cat:mst Axis In Cancer Metabolic Remodelingmentioning

confidence: 99%

See 2 more Smart Citations

Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer

Hipólito

Nunes

Vicente³

et al. 2020

Molecules

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“…Furthermore, CBS up-regulation has been detected in cancer cells including colon cancer, ovarian cancer and lung cancer, amongst others [ 2 , 8 , 18 , 19 , 20 , 21 ]. Under these conditions, tumor growth is facilitated through stimulation of cellular bioenergetics, cell proliferation and angiogenesis [ 2 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Screening of Heteroaromatic Scaffolds against Cystathionine Beta-Synthase Enables Identification of Substituted Pyrazolo[3,4-c]Pyridines as Potent and Selective Orthosteric Inhibitors

et al. 2020

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Cystathionine β-synthase (CBS) is a key enzyme in the production of the signaling molecule hydrogen sulfide, deregulation of which is known to contribute to a range of serious pathological states. Involvement of hydrogen sulfide in pathways of paramount importance for cellular homeostasis renders CBS a promising drug target. An in-house focused library of heteroaromatic compounds was screened for CBS modulators by the methylene blue assay and a pyrazolopyridine derivative with a promising CBS inhibitory potential was discovered. The compound activity was readily comparable to the most potent CBS inhibitor currently known, aminoacetic acid, while a promising specificity over the related cystathionine γ-lyase was identified. To rule out any possibility that the inhibitor may bind the enzyme regulatory domain due to its high structural similarity with cofactor s-adenosylmethionine, differential scanning fluorimetry was employed. A sub-scaffold search guided follow-up screening of related compounds, providing preliminary structure-activity relationships with respect to requisites for efficient CBS inhibition by this group of heterocycles. Subsequently, a hypothesis regarding the exact binding mode of the inhibitor was devised on the basis of the available structure-activity relationships (SAR) and a deep neural networks analysis and further supported by induced-fit docking calculations.

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Functional Materials for Subcellular Targeting Strategies in Cancer Therapy: Progress and Prospects

Cheng,

Qu,

Jiang

et al. 2023

Advanced Materials

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Neoadjuvant and adjuvant therapies have made significant progress in cancer treatment. However, tumor adjuvant therapy still faces challenges due to the intrinsic heterogeneity of cancer, genomic instability, and the formation of an immunosuppressive tumor microenvironment. Functional materials possess unique biological properties such as long circulation times, tumor‐specific targeting, and immunomodulation. The combination of functional materials with natural substances and nanotechnology has led to the development of smart biomaterials with multiple functions, high biocompatibilities, and negligible immunogenicities, which can be used for precise cancer treatment. Recently, subcellular structure‐targeting functional materials have received particular attention in various biomedical applications including the diagnosis, sensing, and imaging of tumors and drug delivery. Subcellular organelle‐targeting materials can precisely accumulate therapeutic agents in organelles, considerably reduce the threshold dosages of therapeutic agents, and minimize drug‐related side effects. This review provides a systematic and comprehensive overview of the research progress in subcellular organelle‐targeted cancer therapy based on functional nanomaterials. Moreover, it explains the challenges and prospects of subcellular organelle‐targeting functional materials in precision oncology. We believe that our review will serve as an excellent cutting‐edge guide for researchers in the field of subcellular organelle‐targeted cancer therapy.This article is protected by copyright. All rights reserved

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Hydrogen Sulfide Metabolism and Signaling in the Tumor Microenvironment

Cited by 39 publications

References 127 publications

Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer

Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer

Screening of Heteroaromatic Scaffolds against Cystathionine Beta-Synthase Enables Identification of Substituted Pyrazolo[3,4-c]Pyridines as Potent and Selective Orthosteric Inhibitors

Functional Materials for Subcellular Targeting Strategies in Cancer Therapy: Progress and Prospects

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