Smilax china root extract as a novel Glucose- 6-phosphate dehydrogenase inhibitor for the treatment of hepatocellular carcinoma

Kanwal, Lubna; Ali, Shaukat; Rasul, Azhar; Tahir, Hafız Muhammad

doi:10.1016/j.sjbs.2022.103400

Cited by 7 publications

(3 citation statements)

References 34 publications

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“…Design strategy.-The principle of versatile electrochemical platform for GSH detection and its Boolean logic application in related biological pathways is shown in Scheme 1, as follows: (1) GSH with three charged functional groups (carboxylates and amines) serves as a bioorganic ligand, and it can chelate strongly with abundant Ag(I) ions due to the thiol functionality; (2) Ag(I) ions as the metal nodes are used to synthesize the complex of GSH and Ag(I) (GSH-Ag(I) complex) via both thiol•••Ag(I) interaction and Ag(I)•••Ag(I) interaction; the complex not only presents abundant positive charge due to the Ag(I) ions, but also possesses a good film-forming ability owing to the Nafion solution; 30 (3) The complex can be attached the GO-modified electrode surface tightly so as to have a better electrocatalytic property on hydrogen peroxide (H 2 O 2 ); this signal output is depended on the ratio of GSH and Ag(I), so the strategy on electrochemical GSH analysis can be designed well by the change of the electrocatalytic signal; (4) In addition, GSH molecules as the biological reaction products are involved in G6PDand GSR-guided biologic processes; 31,32 if the strategy can be employed for exploring the regularities of disease occurrence and development caused by the dysregulation of these processes, this will be beneficial to the development of clinical diagnostics and drug delivery; in consideration of these, four basic and advanced logic gates (YES, AND, AND-AND and AND-AND-AND) are constructed by designing NADPH and GSH as a link point and altering different logic inputs and outputs. We seek to develop these molecular logic triggers which can work well when both or more diseases-associated stimulus exist so as to help to enhance clinical diagnostic and therapeutic accuracy.…”

Section: Resultsmentioning

confidence: 99%

Versatile Electrochemical Platform for GSH Detection and its Boolean Logic Application in Related Biological Pathways

Liu¹,

Ren²,

Hu³

et al. 2022

J. Electrochem. Soc.

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The next-generation advanced molecular devices for clinical diagnostics and biomedical research are of great significance. Herein, a versatile electrochemical platform for glutathione (GSH) detection and its Boolean logic application in related biological pathways are achieved well. At first, GSH-Ag(I) complex is synthesized simply and greenly by controlling properly the ratio of GSH and Ag(I). The complex can be attached onto the graphene oxide (GO)-modified electrode with the assistance in Nafion, presenting an excellent electrocatalytic activity to H2O2. Under optimum conditions, the biosensor can be used for quantitative analysis of GSH with a linear range from 0.001 to 50 μM and the detection limit is about 0.63 nM. Meanwhile, GSH is the reaction product in glutathione reductase (GSR)-based enzyme system in the help of NADPH molecules, and NADPH is a glucose 6-phosphate dehydrogenase (G6PD) catalytic reaction product. In view of these, some basic and advanced logic gates (YES, AND, AND-AND, and AND-AND-AND) are constructed orderly, and these Boolean logic switches on GSH-based biological pathways are developed reasonably. Undoubtedly, the new biosensor can be extended for the diagnosis and treatment of GSH-related diseases, affording accurate diagnosis and therapy.

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Section: Resultsmentioning

confidence: 99%

Versatile Electrochemical Platform for GSH Detection and its Boolean Logic Application in Related Biological Pathways

Liu¹,

Ren²,

Hu³

et al. 2022

J. Electrochem. Soc.

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“…G6PD is known to promote HCC cell proliferation, invasion, migration and inhibit ferroptosis. Knockdown G6PD or inhibit it with smilax China root extract could suppresses HCC cell growth, tumorigenesis and metastasis ( 39 – 41 ). CDCA8, a crucial regulator of mitosis, is upregulated in numerous cancer types.…”

Section: Discussionmentioning

confidence: 99%

Identification of PANoptosis-related subtypes, construction of a prognosis signature, and tumor microenvironment landscape of hepatocellular carcinoma using bioinformatic analysis and experimental verification

Ouyang,

Li,

Wei

et al. 2024

Front. Immunol.

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BackgroundHepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. PANoptosis is a recently unveiled programmed cell death pathway, Nonetheless, the precise implications of PANoptosis within the context of HCC remain incompletely elucidated.MethodsWe conducted a comprehensive bioinformatics analysis to evaluate both the expression and mutation patterns of PANoptosis-related genes (PRGs). We categorized HCC into two clusters and identified differentially expressed PANoptosis-related genes (DEPRGs). Next, a PANoptosis risk model was constructed using LASSO and multivariate Cox regression analyses. The relationship between PRGs, risk genes, the risk model, and the immune microenvironment was studies. In addition, drug sensitivity between high- and low-risk groups was examined. The expression profiles of these four risk genes were elucidate by qRT-PCR or immunohistochemical (IHC). Furthermore, the effect of CTSC knock down on HCC cell behavior was verified using in vitro experiments.ResultsWe constructed a prognostic signature of four DEPRGs (CTSC, CDCA8, G6PD, and CXCL9). Receiver operating characteristic curve analyses underscored the superior prognostic capacity of this signature in assessing the outcomes of HCC patients. Subsequently, patients were stratified based on their risk scores, which revealed that the low-risk group had better prognosis than those in the high-risk group. High-risk group displayed a lower Stromal Score, Immune Score, ESTIMATE score, and higher cancer stem cell content, tumor mutation burden (TMB) values. Furthermore, a correlation was noted between the risk model and the sensitivity to 56 chemotherapeutic agents, as well as immunotherapy efficacy, in patient with. These findings provide valuable guidance for personalized clinical treatment strategies. The qRT−PCR analysis revealed that upregulated expression of CTSC, CDCA8, and G6PD, whereas downregulated expression of CXCL9 in HCC compared with adjacent tumor tissue and normal liver cell lines. The knockdown of CTSC significantly reduced both HCC cell proliferation and migration.ConclusionOur study underscores the promise of PANoptosis-based molecular clustering and prognostic signatures in predicting patient survival and discerning the intricacies of the tumor microenvironment within the context of HCC. These insights hold the potential to advance our comprehension of the therapeutic contribution of PANoptosis plays in HCC and pave the way for generating more efficacious treatment strategies.

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“…RRx-001 demonstrated anticancer effects by inhibiting the activity of G6PD [ 221 ]. In addition to small molecules, several plant extracts have also been identified to have anti-cancer properties that are accompanied by the inhibition of the activity of G6PD [ 222 , 223 ].…”

Section: Pharmacological Targetsmentioning

confidence: 99%

The Role of Reprogrammed Glucose Metabolism in Cancer

Ediriweera

Jayasena

2023

Metabolites

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Cancer cells reprogram their metabolism to meet biosynthetic needs and to adapt to various microenvironments. Accelerated glycolysis offers proliferative benefits for malignant cells by generating glycolytic products that move into branched pathways to synthesize proteins, fatty acids, nucleotides, and lipids. Notably, reprogrammed glucose metabolism and its associated events support the hallmark features of cancer such as sustained cell proliferation, hijacked apoptosis, invasion, metastasis, and angiogenesis. Overproduced enzymes involved in the committed steps of glycolysis (hexokinase, phosphofructokinase-1, and pyruvate kinase) are promising pharmacological targets for cancer therapeutics. In this review, we summarize the role of reprogrammed glucose metabolism in cancer cells and how it can be manipulated for anti-cancer strategies.

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Smilax china root extract as a novel Glucose- 6-phosphate dehydrogenase inhibitor for the treatment of hepatocellular carcinoma

Cited by 7 publications

References 34 publications

Versatile Electrochemical Platform for GSH Detection and its Boolean Logic Application in Related Biological Pathways

Versatile Electrochemical Platform for GSH Detection and its Boolean Logic Application in Related Biological Pathways

Identification of PANoptosis-related subtypes, construction of a prognosis signature, and tumor microenvironment landscape of hepatocellular carcinoma using bioinformatic analysis and experimental verification

The Role of Reprogrammed Glucose Metabolism in Cancer

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