Current Enzyme Inhibition最新文献

{"title":"Uncompetitive inhibition of polyol pathway enzymes by Daucus carota Linn. extract and management of diabetes mellitus","authors":"M. Kazeem, H. Bankole, A. Fatai, Temitope Samson Oguntubi, A. Kappo","doi":"10.2174/1573408019666230613114052","DOIUrl":"https://doi.org/10.2174/1573408019666230613114052","url":null,"abstract":"\u0000\u0000The growing occurrence of complications associated with diabetes calls for the unending exploration of natural products for more efficient therapeutic substances. The polyol pathway is a foundational scheme involved in the development of diabetic complications. Retarding the activities of enzymes in the polyol pathway is, therefore, a potent method of managing these complications.\u0000\u0000\u0000\u0000This work assessed the ability of four non-leafy vegetables, namely Daucus carota Linn. (carrot), Abelmoschus esculentus (L.) Moench (okra), Allium cepa Linn. (onion), and Lycopersicon esculentum Mill. (tomato), to inhibit the activities of aldose reductase and sorbitol dehydrogenase.\u0000\u0000\u0000\u0000The vegetables’ ability was evaluated by incubating the vegetables with suitable enzymes and substrates. Sample(s) with the lowest inhibitory concentration (IC50) was utilized to determine the mechanism of action of the enzymes by constructing the Lineweaver-Burk graph.\u0000\u0000\u0000\u0000Results showed that the aqueous extract of carrot exhibited the lowest IC50 value for the inhibition of both aldose reductase (135.17 µg/mL) and sorbitol dehydrogenase (14.64 µg/mL), respectively. The double reciprocal plot also showed that the aqueous extract of carrot inhibited both aldose reductase and sorbitol dehydrogenase in an uncompetitive fashion.\u0000\u0000\u0000\u0000Aqueous extract of carrot successfully retarded the action of polyol pathway enzymes, which may result in the recovery of diabetic complications. This activity may due to the availability of phytochemicals, including carotenoids and phenylacetylenes.\u0000","PeriodicalId":35405,"journal":{"name":"Current Enzyme Inhibition","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44689991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updates on the Interactions of Herbs Constituents with Cytochrome P450 Drug Metabolizing Enzymes","authors":"Ahmed H Arbab, Elwaleed E. Zaroug, Tarig Omer Ahmed, Mahmoud M. E. Mudawi","doi":"10.2174/1573408019666230601121657","DOIUrl":"https://doi.org/10.2174/1573408019666230601121657","url":null,"abstract":"\u0000\u0000Cytochrome P450 enzymes are the main drug-metabolizing enzyme, and their activity is influenced by numerous factors, including several plants’ constituents. Herbal products mediated induction or inhibition of cytochrome P450 leads to a change in drug metabolism and consequently, drug bioavailability, safety, therapeutic efficacy, and herb-drug interaction. Since herbal preparations are commonly used either alone or concomitantly with conventional drugs, understanding the interactions of plant constituents with cytochrome P450 is crucial. Therefore, this review highlighted plants with significant inhibition, induction, or modulatory /contradictory effects on human and animal cytochrome P450 enzymes. An extensive literature search was conducted on PubMed, ScienceDirect, and Google Scholar databases to identify relevant literature. About sixty medicinal plants with significant interaction with cytochrome P450 isoforms were summarized with their common uses and affected cytochrome P450 enzyme isoforms. Besides, representative examples of plant constituents and other factors contributing to plant-induced cytochrome P450 modulation and possible herb-drug interactions were also discussed in this review.\u0000","PeriodicalId":35405,"journal":{"name":"Current Enzyme Inhibition","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46972611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory effect of ascorbic acid on glutathione S-transferase from human erythrocytes","authors":"M. - Erat, Yunus Emre Erat, Ayşe Rümeysa Erat","doi":"10.2174/1573408019666230530095315","DOIUrl":"https://doi.org/10.2174/1573408019666230530095315","url":null,"abstract":"\u0000\u0000Inhibition of certain specific glutathione S-transferase isozymes is associated with the efficacy of chemotherapy in the treatment of cancer patients.\u0000\u0000\u0000\u0000We aimed to determine whether ascorbic acid, which can be used as a drug and antioxidant food supplement, is a glutathione S-transferase isozyme inhibitor.\u0000\u0000\u0000\u0000For this purpose, glutathione S-transferase was first purified from human erythrocytes and the in vitro effect of ascorbic acid on enzyme activity was investigated. Then, kinetic studies were performed to evaluate the inhibition potential of ascorbic acid, which was determined to be an inhibitor of the enzyme.\u0000\u0000\u0000\u0000The enzyme was purified 1286-fold with a yield of 81% and specific activity of 18.00 U/mg protein. The effects of ascorbic acid were tested on the in vitro enzyme activity of glutathione S-transferase and detected to be an inhibitor for the enzyme with 10 mM of IC50 value. Ki constants and inhibition type were also determined for the enzyme.\u0000\u0000\u0000\u0000This finding indicates that ascorbic acid can be an effective inhibitor of some GST isoenzymes increased in cancer cells. Abundant ascorbic acid intake may prevent cancer formation by strengthening the antioxidant defense system, on the other hand, it may increase the effectiveness of cancer treatment by inhibiting the chemotherapy-resistant GST enzyme.\u0000","PeriodicalId":35405,"journal":{"name":"Current Enzyme Inhibition","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42486175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoscutellarein from Bixa orellana leaves uncompetitively inhibits recombinant human aldose reductase and prevents sorbitol accumulation and lens opacity","authors":"Sreedhar Bodiga, Mohan Krishna Durgam, V. Bodiga, P. Vemuri","doi":"10.2174/1573408019666230517142826","DOIUrl":"https://doi.org/10.2174/1573408019666230517142826","url":null,"abstract":"\u0000\u0000Enhanced aldose reductase activity results in increased accumulation of sorbitol. Therefore, inhibition of aldose reductase is an effective strategy to prevent or delay certain diabetic complications.\u0000\u0000\u0000\u0000Various extracts of the leaves of B. orellana were tested for their inhibitory activity on the aldose reductase. Ethyl acetate extract that showed maximum inhibition was further fractionated and the inhibitor was identified as isoscutellarein by spectroscopic methods. IC50 of recombinant human aldose reductase by isoscutellarein was found to be 14 M and the mode of inhibition was uncompetitive with a decrease in both Km and Vmax. Isoscutellarein was bound to the active site of aldose reductase (3RX3), namely to Ala-299, Leu-300, Leu-301, His-110 and Tyr-48.\u0000\u0000\u0000\u0000Docking results exhibited a binding energy of -9.15 kJ/mol.\u0000\u0000\u0000\u0000The incubation of red blood cells with high glucose concentrations mimicking hyperglycemic conditions promoted sorbitol accumulation, which was effectively inhibited by isoscutellarein. Further, xylose-induced opacity of the lens was effectively inhibited by isoscutellarein.\u0000","PeriodicalId":35405,"journal":{"name":"Current Enzyme Inhibition","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44841670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Lactobacillus rhamnosus and Diclofenac with Curcumin for neuronal restoration and repair against Scopolamine induced Dementia in Zebrafish (Danio rerio)","authors":"Sonali Pande, Chirag Patel","doi":"10.2174/1573408019666230508155702","DOIUrl":"https://doi.org/10.2174/1573408019666230508155702","url":null,"abstract":"\u0000\u0000Clinical studies have already revealed the ubiquitous neuroprotective role of curcumin in neuronal deterioration, but it cannot be used alone due to its truncated bioavailability. Currently, many such approaches are functional, which overcome this issue either by increasing the solubility or absorption. These approaches carry a costlier treatment. One more tactic is present but less focused i.e., by limiting the intestine and liver enzymatic metabolism; by this approach, curcumin will be more available for its beneficial outcome.\u0000\u0000\u0000\u0000The goal of this study was to evaluate the impact of Lactobacillus rhamnosus and diclofenac on the neuroprotective effects of curcumin against scopolamine-induced dementia.\u0000\u0000\u0000\u0000Physical parameters involved a novel tank test, T maze test, whereas neurochemical parameters include brain oxidative stress and acetylcholinesterase (Ache) inhibition activity in a zebrafish dementia model.\u0000\u0000\u0000\u0000Our results demonstrated that curcumin with Lactobacillus rhamnosus and diclofenac significantly (p<0.05) reduced anxiety, memory deficits, and brain oxidative stress compared to the alone curcumin-treated group.\u0000\u0000\u0000\u0000This result approves that curcumin with L.rhamnosus and diclofenac have superior activity compared to curcumin alone. However, further clinical studies are needed to validate these findings\u0000","PeriodicalId":35405,"journal":{"name":"Current Enzyme Inhibition","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41752798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical constituents’ analysis of Rhanterium adpressum Coss & Durieu flowers extracts and their α-amylase and α-glucosidase inhibition properties","authors":"Boussoussa Hadjer, Benabed Khadidja Houda, Khacheba Ihcen, Yousfi Mohamed","doi":"10.2174/1573408019666230418114015","DOIUrl":"https://doi.org/10.2174/1573408019666230418114015","url":null,"abstract":"\u0000\u0000Rhanterium adpressum is an endemic and desert plant found in Algerian Sahara, it is used by the local population in cheese production and folk medicine as an antidiuretic and antimicrobial.\u0000\u0000\u0000\u0000This study aimed to analyse the phytochemical composition of Rhanterium adpressum extracts by GC-MS and assess their inhibitory potential on α-amylase and α-glucosidase enzymes linked to diabetes.\u0000\u0000\u0000\u0000Two solvents were used for extraction: petroleum ether and dichloromethane. The obtained extracts were then analysed by GC-MS and in vitro tested for their antidiabetic activity.\u0000\u0000\u0000\u0000GC-MS analysis of extracts from R. adpressum flowers revealed various phytocompounds, such as (-)-Spathulenol, alpha.-Amyrin, Lupeol and Cedran-diol in petroleum ether extract; 1H-Cycloprop[e]azulen-7-ol, 5(1H)-Azulenone and alpha-cardinol in dichloromethane extract. Petroleum ether extract exhibited a good in vitro antidiabetic activity in comparison to dichloromethane extract.\u0000\u0000\u0000\u0000This research confirms the antidiabetic activity of petroleum ether extract when compared with dichloromethane extract; other studies are needed for purification and in vivo study of bio-compounds from Rhanterium adpressum. This investigation offers scientific data that flowers of Rhanterium adpressum exhibit in vitro anti-diabetic effect.\u0000","PeriodicalId":35405,"journal":{"name":"Current Enzyme Inhibition","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46186979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-amylase Inhibitory Activity of Extracts from Algerian Calamintha nepeta (L.)","authors":"K. Benabed, Hadjer Boussoussa, Ihcen Khacheba, Abir Bekhaoua, Fatima zohra Douadji, sabrina Daïdi, Souad Djaafour, M. Yousfi","doi":"10.2174/1573408019666230331084001","DOIUrl":"https://doi.org/10.2174/1573408019666230331084001","url":null,"abstract":"\u0000\u0000Calamintha nepeta is a plant from the Lamiaceae family that is known for its traditional use to treat diabetes among Algerian populations. However, till now, there has been no research work to confirm this activity.\u0000\u0000\u0000\u0000Calamintha nepeta is a plant from the Lamiaceae family which is known for its traditional use to treat diabetes in Algerian populations. Until now there have been no research work to confirm this activity.\u0000\u0000\u0000\u0000This work aimed to evaluate the amylase inhibitory activity of essential oils and phenolic compounds from both methanolic and aqueous extracts of Algerian Calamintha nepeta (L.).\u0000\u0000\u0000\u0000The evalutation of the antiamylatic activity of essential oil, methanolic and aqueous extracts from Algerian Calamintha nepeta (L.).\u0000\u0000\u0000\u0000The essential oil was obtained by hydrodistillation and analyzed using GC and then GC/MS. Aqueous and methanolic extracts were obtained from the remains of the hydrodistillation. Total phenolic compounds were quantified using the Folin-Ciocalteu method. The amylase inhibitory activity of the extracts was determined by testing their ability to inhibit alpha-amylase.\u0000\u0000\u0000\u0000The extraction yield was 0.67 % (w/w) for the essential oil, and 11.85 and 4.38 % (w/w) for the aqueous and methanolic extracts, respectively. The essential oil analysis revealed that menthone, menthol, pulegone, and pulegone oxide were the main components of the oil. The total phenolic compounds in the aqueous and methanolic extracts were 41.81 and 32.92 mg GAE/g DW, respectively. The extracts inhibited α-amylase activity with IC50 values of 24.46, 31.54, and 115.47 mg/ml for the methanolic extract, essential oil, and aqueous extract, respectively.\u0000\u0000\u0000\u0000Extraction yield was 0.67 %(w/w) for the essential oil, and 11.85 and 4.38 %(w/w) for the aqueous and methanolic extracts respectively. The essential oil analysis revealed that menthone, menthol, pulegone and pulegone oxide were the main components. Total phenolic compounds for the aqueous and methanolic extracts were respectively 41.81 and 32.92 mg GAE/g. The different extracts showed inhibition activity towards α-amylase with IC50 values equal to : 24.46 ; 31.54 and 115.47mg/ml for the methanolic extract, the essential oil and the aqueous extract respectively.\u0000\u0000\u0000\u0000The different extracts of Calamintha nepeta showed an interesting composition and significant amylase inhibitory activity, emphasizing their successful use in traditional medicine.\u0000\u0000\u0000\u0000The different extracts of Calamintha nepeta showed an interesting composition, and a significant antimaylatic activity.\u0000\u0000\u0000\u0000future profound studies are necessary to identify the active molecules\u0000","PeriodicalId":35405,"journal":{"name":"Current Enzyme Inhibition","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42053951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory Activity of Pyrazole Analogues Deduced from Bioactive Piperine: Synthesis, in silico, and in vitro Evaluation","authors":"I. Kaliappan, Lilbet Mathew, Murugesan Sankaranarayanan","doi":"10.2174/1573408019666230303143432","DOIUrl":"https://doi.org/10.2174/1573408019666230303143432","url":null,"abstract":"\u0000\u0000Around ten novel pyrazoline and pyrazolidine derivatives were designed and synthesized by the condensation of piperine, hydrazine hydrate, phenylhydrazine, aromatic carboxylic acid, and ethanol.\u0000\u0000\u0000\u0000Around ten novel pyrazoline and pyrazolidine derivatives were designed, synthesized by the condensation of piperine, hydrazine hydrate, phenyl hydrazine, aromatic carboxylic acid and ethanol.\u0000\u0000\u0000\u0000The synthesized compounds (2, 3, 4a-d, and 5a-d) were characterized by FTIR, 1HNMR, mass spectral, and elemental analysis. Pharmacokinetic, physicochemical, drug-likeness, and medicinal chemistry friendliness parameters were also predicted by in silico methods.\u0000\u0000\u0000\u0000In silico docking studies and synthesized compounds, in vitro biological evaluation\u0000\u0000\u0000\u0000Furthermore, compounds were screened for in vitro anti-inflammatory activity by the HRBC membrane stabilization method using diclofenac sodium as the standard drug. The tested compounds showed moderate anti-inflammatory activity compared to the standard drug. The molecular docking studies of significantly active (4d) and least active compounds (5d) were also carried out in the active sites of an arachidonate-12-lipoxygenase target in order to study the putative binding pattern of the study compounds.\u0000\u0000\u0000\u0000The synthesized compounds (2, 3, 4a-d and 5a-d) were characterized by FTIR, 1HNMR, Mass spectral and elemental analysis. Pharmacokinetic, physico-chemical, drug likeness and medicinal chemistry friendliness parameters were also predicted by in silico methods.\u0000\u0000\u0000\u0000According to the findings of this study, further lead identification as well as lead optimization techniques will be required in the near future in order to get potent analogues.\u0000\u0000\u0000\u0000- Further, the compounds were screened for in vitro anti-inflammatory activity by HRBC membrane stabilization method using Diclofenac Sodium as standard drug. The tested compounds showed moderate anti-inflammatory activity compared to the standard drug. The molecular docking studies of significantly active (4d) and least active compound (5d) was also carried out in the active sites of Arachidonate-12-lipoxygenase target in order to study the putative binding pattern of the study compounds.\u0000\u0000\u0000\u0000According to the findings of this study, more in-vivo research as well as lead optimization techniques will be required in the near future.\u0000","PeriodicalId":35405,"journal":{"name":"Current Enzyme Inhibition","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41409630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HGF/c-MET: A Potential Target for the Treatment of Various Cancers","authors":"S. Bhatt, Kuttiappan Anitha, K. Dua, D. Chellappan, G. Gupta, Sachin Kumar Singh, Mohana Lakshmi Sabapathi","doi":"10.2174/1573408019666230227101036","DOIUrl":"https://doi.org/10.2174/1573408019666230227101036","url":null,"abstract":"\u0000\u0000Cancer is the abnormal growth of cells in the body due to an imbalance in the normal apoptotic pathways. The abnormality in the cancer cells makes them malignant. Various types of treatment, including chemotherapy, radiation therapy, targeted therapy, and immunotherapy (IMT), are used for cancer. Mesenchymal-epithelial transition factor (c-Met) belongs to the tyrosine kinase receptor family and is overexpressed in various types of cancers. c-Met is a proto-oncogene and facilitates a wide range of biological functions, including cell proliferation, growth, migration, invasion, and angiogenesis, through interaction with its sole ligand hepatocyte growth factor (HGF). Currently, various c-mesenchymal-epithelial transition (c-MET) inhibitors and antibodies are in human trials for their anti-cancer activity.\u0000\u0000\u0000\u0000The c-MET is a kinase receptor for hepatocyte growth factor (HGF). It is well-recognized for its tumorigenic potential. HGF binding with c-Met leads to c-Met dimerization and c-Met phosphorylation, which in turn activates many intracellular signalling pathways, including ERK1/2, MAPK, STAT3, Rac1, and PI3K/AKT. These pathways regulate the proliferation, invasion, and migration of cancer cells. Upon binding of HGF to c-MET, a series of phosphorylation reactions get started, which leads to transcription and translation of various proteins, followed by abnormal growth of cancerous tissues due to dysregulation of the cell cycle. The HGF/c-MET signalling pathways have shown their potential in the development of many cancers, including gastric cancer (GC). Several clinical trials have evaluated the therapeutic benefits of MET-targeted therapies involving various agents, such as anti-MET antibodies, anti-HGF antibodies, and tyrosine kinase inhibitors (TKIs). Various c-MET inhibitors are in clinical trials. The current review is focussed on the critical role of the HGF/c-MET pathways in the progression of various cancers, including GC. In addition, this review will also focus on the combination potential of c-MET inhibitors with immuno-oncology drugs, such as programmed cell death protein 1 (PD-1) inhibitors, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, tumor necrosis factor (TNF) receptor (OX-40) agonists, etc.\u0000\u0000\u0000\u0000The method adopted for the study was primarily based on the secondary search through a systematic review of the literature.\u0000\u0000\u0000\u0000A study of recent literature and various preclinical and human trials suggests the effectiveness of c-MET inhibitors (alone or in combination) in different cancer types, including GC. In this paper, the results have been elaborated as to how many papers/manuscripts/publications on the topic are present, how many drugs are in Phase I/II/ III/RCT, etc., and that how many papers report on the clinical outcomes of which agent/drug (mentioned in percentage).\u0000\u0000\u0000\u0000The use of c-MET inhibitors and antibodies has emerged as a latent therapeutic approach for the treatment of various types of cancer. The c-M","PeriodicalId":35405,"journal":{"name":"Current Enzyme Inhibition","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47981939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactions of butyrylcholinesterase with neuroblastoma-associated oncoproteins","authors":"J. Baranowska-Kortylewicz, Z. Kortylewicz, Erin M. McIntyre, J. Sharp, D. Coulter","doi":"10.2174/1573408019666230206151403","DOIUrl":"https://doi.org/10.2174/1573408019666230206151403","url":null,"abstract":"\u0000\u0000Emerging data indicate that BCHE, a gene encoding the enzyme butyrylcholinesterase, is a negative prognostic marker in MYCN-amplified neuroblastoma. Levels of butyrylcholinesterase in children newly diagnosed with neuroblastoma are proportional to MYCN amplification and the response to therapy. To better understand the functions of butyrylcholinesterase in neuroblastoma, we examine interactions of this enzyme with several neuroblastoma-associated kinases and provide in depth review of known associations.\u0000\u0000\u0000\u0000BCHE-deleted cells (KO) were produced from MYCN-amplified BE(2)-C cells (WT) by the CRISPR-Cas9 targeted disruption of the BCHE locus. Activation levels of several oncoproteins and the expression of N-Myc in KO were compared to WT cells. N-Myc protein expression, multiplexed detection of relative protein expression and phosphorylation of 71 tyrosine kinases and 17 proteins in the MAPK pathway were assessed using Western immunoblotting and microarrays in exponentially growing untreated cells and in cells exposed to the genotoxic stress.\u0000\u0000\u0000\u0000BCHE locus disruption and butyrylcholinesterase deficiency result in the loss of N-Myc protein and a significant deactivation of several kinases associated with the aggressive neuroblastoma phenotype as well as major changes in the phosphorylation of upstream and downstream partners of these kinases.\u0000\u0000\u0000\u0000Butyrylcholinesterase appears to contribute to the activation of several pathways in MYCN-amplified cells including FGF-R1, Ltk, TrkB, and Ros1. Deletion of BCHE and ensuing butyrylcholinesterase deficit deactivate these pathways suggesting the role of BChE as a novel druggable target in neuroblastoma therapy.\u0000","PeriodicalId":35405,"journal":{"name":"Current Enzyme Inhibition","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47902688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}