Journal of receptor and signal transduction research最新文献

The role of G protein-coupled receptor 4 in inflammatory diseases and its potential clinical significance. G蛋白偶联受体4在炎症性疾病中的作用及其潜在的临床意义

Journal of receptor and signal transduction research Pub Date : 2025-07-06 DOI: 10.1080/10799893.2025.2529174

Qilimuge Bai, Gegentuya Bao, Yali Yan, Saqirina Hereid, Xiaohong Bai, Liang Bao

引用次数: 0

A novel anticancer candidate, coumarin-3-carboxamide derivative inhibits cell proliferation and migration in MDA-MB-231 cell line. 香豆素-3-羧酰胺衍生物是一种新的抗癌候选物质，可抑制MDA-MB-231细胞株的细胞增殖和迁移。

Journal of receptor and signal transduction research Pub Date : 2025-06-02 DOI: 10.1080/10799893.2025.2513696

Sevide Sencan, Hulya Celik Onar

{"title":"A novel anticancer candidate, coumarin-3-carboxamide derivative inhibits cell proliferation and migration in MDA-MB-231 cell line.","authors":"Sevide Sencan, Hulya Celik Onar","doi":"10.1080/10799893.2025.2513696","DOIUrl":"https://doi.org/10.1080/10799893.2025.2513696","url":null,"abstract":"Breast cancer is one of the leading cancer types in terms of morbidity and mortality worldwide. Although developing technology, early diagnosis and treatment opportunities provide positive contributions to the treatment of breast cancer, research on new drugs that are less toxic to healthy cells, safer and more effective for cancer cells, increasing the quality of life of the patient is still ongoing. Coumarin and its derivatives have been shown great interest to develop safer and more effective anticancer drugs. Therefore, we investigated the anticancer activity of novel coumarin-3-carboxamide derivative 3i in MDA-MB-231 cells. We found that coumarin-3-carboxamide derivative 3i inhibited cell proliferation, colony formation and migration. However, coumarin-3-carboxamide derivative 3i did not induce apoptosis and autophagy. Consequently, our findings suggest for the first time that novel coumarin-3-carboxamide 3i has anticancer activity and may be an important drug candidate for the treatment of triple-negative breast cancer. Further investigations are required to elucidate its impact on breast cancer.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201330","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}

引用次数: 0

Determination of cytokine profile and associated genes of the signaling pathway in HNSCC. HNSCC细胞因子谱及信号通路相关基因的测定。

IF 2.8

Journal of receptor and signal transduction research Pub Date : 2022-10-01 Epub Date: 2021-12-09 DOI: 10.1080/10799893.2021.2013888

Aysel Kalayci Yigin, Ali Azzawri, Kayhan Ozturk, Tulin Cora, Mehmet Seven

{"title":"Determination of cytokine profile and associated genes of the signaling pathway in HNSCC.","authors":"Aysel Kalayci Yigin, Ali Azzawri, Kayhan Ozturk, Tulin Cora, Mehmet Seven","doi":"10.1080/10799893.2021.2013888","DOIUrl":"https://doi.org/10.1080/10799893.2021.2013888","url":null,"abstract":"Head and neck squamose cell carcinoma (HNSCC) is an aggressive group of tumors that are generally heterogeneous. Despite treatment advances, disease-free survival has not significantly improved. Therefore, it is of great importance to understand the molecular etiology of HNSCC and genetic alterations in the signal pathways in order to develop new therapeutic approaches. In this study, firstly we used a cytokine array to analyze the secretomes of HNSCC patients and healthy controls. In the next step, the results from the cytokine sequence were validated by qRT-PCR and western blot, including genes in the associated signaling pathway. In array analysis, the levels of EGF, IGF-1, IGFBP-1, and PDGFBB were significantly higher in patients than in the controls. The results of qRT-PCR analyses showed that expression levels of PDGFRB gene were significantly up-regulated (p = 0.006) and PTEN (p > 0.001) were significantly down-regulated in tumors compared with normal tissues. When groups (early vs. advanced) were compared, higher expression of IGFBP-1 was observed in the larynx (p = 0.045) and larynx + oral cavity tumors (p = 0.010) in an advanced stage. In western blot analysis, pEGFR, pIGF-IR, pIR-β, pPDGFRB, and pAKT levels were upregulated, and pPTEN was downregulated in tumors. Based on our observations, determining the interactions of EGFR, PDGFRB, IGF-1R and PTEN or the activation of each might represent a promising new and innovative treatment approach in HNSCC patients. It seems clear that, in most cancers, effective targeted therapy may be involved the blockade of each one or multiple targets.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"462-468"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39821902","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}

引用次数: 0

Integrated computational approach for in silico design of new purinyl pyridine derivatives as B-Raf kinase inhibitors. 新型嘌呤基吡啶衍生物B-Raf激酶抑制剂的集成计算机设计方法。

IF 2.8

Journal of receptor and signal transduction research Pub Date : 2022-10-01 Epub Date: 2021-11-29 DOI: 10.1080/10799893.2021.1999472

Vinutha Kuchana, Vaeshnavi Kashetti, Sai Kiran Reddy Peddi, Sreekanth Sivan, Vijjulatha Manga

{"title":"Integrated computational approach for in silico design of new purinyl pyridine derivatives as B-Raf kinase inhibitors.","authors":"Vinutha Kuchana, Vaeshnavi Kashetti, Sai Kiran Reddy Peddi, Sreekanth Sivan, Vijjulatha Manga","doi":"10.1080/10799893.2021.1999472","DOIUrl":"https://doi.org/10.1080/10799893.2021.1999472","url":null,"abstract":"B-Raf is one among the most frequently mutating proto-oncogene which is associated with the serine/threonine Raf kinase family involved in the RAS-RAF-MEK-ERK pathway, which is the most deregulated pathway in human cancers. Mutant B-Raf V600E got an excellent scope for investigation in cancer as a potential therapeutic target. Formerly B-RafV600E is considered the molecular target for numerous antitumor compounds like purinyl pyridine and pyrimidine derivatives. In the current research work using molecular docking approach of Schrodinger Glide 5.6 version, ligand docking, pharmacophore-based virtual screening, binding free energy calculations of a series of 2-amino purinyl pyridine and pyrimidine derivatives were modeled, their docking values were predicted, that were considered to be potent against B-Raf V600E. A five-point hypothesis accompanied by a hydrogen bond acceptor(A), two hydrogen bond donors(D), and two aromatic rings (R) was built with a justifiable R2 value of 0.91 and a Q2 value of 0.64. Then by using Asinex Elite Synergy database, virtual screening was performed, and identified several potential hits. Subsequently, the molecules which had interactions with the target B-Raf kinase were determined by subjecting the obtained hits for SP and XP docking processes. Finally, for the top leads obtained, binding free energies were accomplished. About 16 new purinyl pyridine molecules were also designed. Almost nine molecules manifested crucial ligand interactions and binding free energies. At the outset, this research paved the way for us in spotting new molecules with B-Raf inhibitory activity, which can further be explored to design molecules with enhanced pharmacokinetic profiles.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"439-453"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39677280","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}

引用次数: 2

Target-based in-silico screening of basil polysaccharides against different epigenetic targets responsible for breast cancer. 罗勒多糖对乳腺癌不同表观遗传靶标的靶向性筛选。

IF 2.8

Journal of receptor and signal transduction research Pub Date : 2022-10-01 Epub Date: 2022-07-21 DOI: 10.1080/10799893.2022.2058016

Nancy Bhura, Pawan Gupta, Jeena Gupta

{"title":"Target-based in-silico screening of basil polysaccharides against different epigenetic targets responsible for breast cancer.","authors":"Nancy Bhura, Pawan Gupta, Jeena Gupta","doi":"10.1080/10799893.2022.2058016","DOIUrl":"https://doi.org/10.1080/10799893.2022.2058016","url":null,"abstract":"Purpose: Breast cancer (BC) is one of the leading types of cancer found in women. One of the causes reported for BC is improper regulation of epigenetic modifications. Various epigenetic targets such as histone deacetylases (HDAC) and histone acetyltransferases (HAT) regulate many types of cancer, including BC. Basil is known to possess anti-cancer properties; however, the role of its polysaccharides against different epigenetic targets is still not very clear. Therefore, the molecular docking method is used to find out the binding potential of the BPSs against different epigenetic targets responsible for BC.Methods: All the basil polysaccharides (BPSs) were screened against the diverse epigenetic targets reported for BC (HDAC1-2, 4-8, and HAT) using molecular docking studies alongwith swissADME studies to check the drug likeliness of the BPSs.Results: It was found that glucosamine ring, glucosamine linear, glucuronic acid linear, rhamnose linear, glucuronic acid ring, galactose ring, mannose, glucose, and xylose were exhibited consistent binding potential against the epigenetic targets (HDAC1, HDAC2, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, and HAT,) responsible for BC.Conclusion: This is the first report where BPSs were reported against these epigenetic targets. These studies can help to understand the underlying mechanism of BPSs used against epigenetic targets for BC. These results can be further validated experimentally to confirm their potential as a promising inhibitor against the epigenetic targets (HDAC1-2, 4-8, and HAT) having a role in BC.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"521-530"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40610971","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}

引用次数: 0

PPARγ activation by pioglitazone enhances the anti-proliferative effects of doxorubicin on pro-monocytic THP-1 leukemia cells via inducing apoptosis and G2/M cell cycle arrest. 吡格列酮激活PPARγ通过诱导凋亡和G2/M细胞周期阻滞增强阿霉素对单核细胞前THP-1白血病细胞的抗增殖作用。

IF 2.8

Journal of receptor and signal transduction research Pub Date : 2022-10-01 Epub Date: 2021-10-13 DOI: 10.1080/10799893.2021.1988972

Hassan Ghasemi, Ali Jamshidi, Mohammad Amin Ghatee, Komeil Mazhab-Jafari, Milad Khorasani, Mina Rahmati, Saeed Mohammadi

{"title":"PPARγ activation by pioglitazone enhances the anti-proliferative effects of doxorubicin on pro-monocytic THP-1 leukemia cells via inducing apoptosis and G2/M cell cycle arrest.","authors":"Hassan Ghasemi, Ali Jamshidi, Mohammad Amin Ghatee, Komeil Mazhab-Jafari, Milad Khorasani, Mina Rahmati, Saeed Mohammadi","doi":"10.1080/10799893.2021.1988972","DOIUrl":"https://doi.org/10.1080/10799893.2021.1988972","url":null,"abstract":"Purpose: Doxorubicin (DOX) is a common chemotherapeutic agent, with toxic side effects, and chemoresistance. Combination chemotherapy is a successful approach to overcome these limitations. Here, we investigated the effects of pioglitazone (PGZ), a PPARγ agonist, and/or DOX on the viability, cell cycle, apoptosis on THP-1 cells and normal human monocytes (NHMs).Methods: MTT assay was used to evaluate the cytotoxicity of DOX and/or PGZ. Cell cycle progression and apoptosis induction were examined by PI or Annexin V-PI double staining, and analyzed by flow cytometry. Quantitative RT-PCR was used to evaluate the changes in the mRNA expression of cell cycle progression or apoptosis-associated genes including P27, P21, CDK2, P53, BCL2 and FasR.Results: DOX, PGZ and DOX + PGZ exerted their cytotoxic effects in a dose- and time-dependent manner with low toxicity on NHMs. The cell growth inhibitory effects of DOX were in association with G2/M arrest, while PGZ executed S phase arrest. PGZ treatment enhanced G2/M among DOX-treated combinations with moderate elevation in the S phase. DOX, PGZ and combined treatments induced apoptosis (mostly late phase) in a dose-dependent manner. All treatments resulted in the significant overexpression of p21, p27, p53 and FasR genes and downregulation of CDK2. DOX + PGZ combined treatments exhibited the most significant changes in mRNA expression.Conclusion: We demonstrated that the antiproliferative, cell cycle regulation and apoptosis-inducing capacity of DOX was enhanced by PGZ in THP-1 leukemia cells in a dose-dependent manner. Therefore, the combination of DOX + PGZ could be used as a novel combination to target AML.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"429-438"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39514651","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}

引用次数: 2

XIST/miR-34a-5p/PDL1 axis regulated the development of lung cancer cells and the immune function of CD8⁺ T cells. XIST/miR-34a-5p/PDL1轴调控肺癌细胞的发育和CD8+ T细胞的免疫功能。

IF 2.8

Journal of receptor and signal transduction research Pub Date : 2022-10-01 Epub Date: 2022-01-23 DOI: 10.1080/10799893.2021.2019274

Jing Li, Liyan Che, Chang Xu, Dongdong Lu, Yan Xu, Mengru Liu, Wenshu Chai

{"title":"XIST/miR-34a-5p/PDL1 axis regulated the development of lung cancer cells and the immune function of CD8+ T cells.","authors":"Jing Li, Liyan Che, Chang Xu, Dongdong Lu, Yan Xu, Mengru Liu, Wenshu Chai","doi":"10.1080/10799893.2021.2019274","DOIUrl":"https://doi.org/10.1080/10799893.2021.2019274","url":null,"abstract":"Purpose: Long non-coding RNA (lncRNA) XIST has been shown to be involved in the immune escape of breast cancer, but it is unclear whether it is involved in the immune escape of lung cancer, so it will be discussed in this study.Methods: XIST and miR-34a-5p expression in lung cancer tissues and cells were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The targeting relationship between miR-34a-5p and XIST/programmed cell death receptor ligand 1 (PDL1) was predicted by bioinformatics website and verified by dual-luciferase report experiment. After co-transfection with XIST specific short hairpin RNA (sh-XIST) and miR-34a-5p inhibitors, the changes in PDL1 expression, and cell biological behavior were detected by qRT-PCR, cell counting kit 8, flow cytometry, and Transwell experiments. Similarly, after co-transfection of PDL1 specific small interfering RNA (siPDL1) and miR-34a-5p inhibitors, the changes in cell biological behavior were detected again. After CD8+ T cells were co-cultured with lung cancer cells transfected with sh-XIST and miR-34a-5p inhibitors, the expression of cytokines and immunosuppressive molecules was detected by western blot and enzyme-linked immunosorbent assay (ELISA).Results: XIST was up-regulated in lung cancer tissues, while miR-34a-5p was the opposite. XIST up-regulated the expression of PDL1 by targeting miR-34a-5p, thereby affecting the viability, apoptosis, migration, and invasion of lung cancer cells. In the co-culture system, XIST targeted miR-34a-5p to inhibit cytokines secretion and promote the expression of immunosuppressive molecules.Conclusions: XIST/miR-34a-5p/PDL1 axis was involved in the malignant biological behavior of lung cancer cells and the immune function of CD8+ T cells.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"469-478"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39850416","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}

引用次数: 9

GLP-1 agonist liraglutide improves ouabain-induced mania and depressive state via GSK-3β pathway. GLP-1激动剂利拉鲁肽通过GSK-3β途径改善瓦阿因诱导的躁狂和抑郁状态。

IF 2.8

Journal of receptor and signal transduction research Pub Date : 2022-10-01 Epub Date: 2022-02-08 DOI: 10.1080/10799893.2022.2032747

Mustafa Nusret Çiçekli, Emre Soner Tiryaki, Ahmet Altun, Caner Günaydın

{"title":"GLP-1 agonist liraglutide improves ouabain-induced mania and depressive state via GSK-3β pathway.","authors":"Mustafa Nusret Çiçekli, Emre Soner Tiryaki, Ahmet Altun, Caner Günaydın","doi":"10.1080/10799893.2022.2032747","DOIUrl":"https://doi.org/10.1080/10799893.2022.2032747","url":null,"abstract":"Bipolar disorder (BD) is a severe mental illness characterized by aberrant mood changes between hypomania and mania or mixed states and depression. Metabolic changes also accompany disease progression and cause significant morbidity. Symptomatic treatment options are available, but asymptomatic patients and poor drug responders are significant problems. Based on the most common pharmacological agent that is used in the treatment, lithium and its main mechanisms of action, oxidative stress, and glycogen synthase kinase-3β (GSK-3β) signaling are extensively investigated. However, knowledge about the effects of compounds that positively affect oxidative stress and GSK-3β signaling, such as glucagon-like peptide-1 (GLP-1) mimetics, liraglutide, is still missing. Therefore, in this study, we aimed to investigate the effects of liraglutide on the ouabain-induced bipolar disease model in rats. After intracerebroventricular single dose ouabain administration, animals were treated with 100, 200, and 400 µg/kg liraglutide (s.c.) and valproic acid (200 mg/kg, i.p.) for 10 d. The locomotion and depressive states of animals were assessed by an open field, forced swimming test, and sucrose preference tests. Serum total antioxidant (TAS) and oxidant states (TOS) and glutathione, malonyl dialdehyde (MDA) levels in the brain tissue were determined. GSK-3β phosphorylation was evaluated by western blotting. Our results demonstrated that liraglutide attenuated ouabain-induced hyperlocomotion and depressive state. Additionally, liraglutide prevented oxidative stress after ouabain administration. Decreased GSK-3β phosphorylation due to the ouabain insult was alleviated by liraglutide treatment. These findings indicate that the manic and depressive-like behaviors are ameliorated by liraglutide, which exerted antioxidant action, possibly improving GSK-3β phosphorylation.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"486-494"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39775957","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}

引用次数: 0

Molecular docking study of britannin binding to PD-L1 and related anticancer pseudoguaianolide sesquiterpene lactones. britannin与PD-L1及相关抗癌伪愈木酚内酯倍半萜内酯结合的分子对接研究。

IF 2.8

Journal of receptor and signal transduction research Pub Date : 2022-10-01 Epub Date: 2021-11-17 DOI: 10.1080/10799893.2021.2003816

Gérard Vergoten, Christian Bailly

{"title":"Molecular docking study of britannin binding to PD-L1 and related anticancer pseudoguaianolide sesquiterpene lactones.","authors":"Gérard Vergoten, Christian Bailly","doi":"10.1080/10799893.2021.2003816","DOIUrl":"https://doi.org/10.1080/10799893.2021.2003816","url":null,"abstract":"The pseudoguaianolide-type sesquiterpene lactone (SL) britannin (BRT), found in different Inula species, has been characterized as a potent anticancer agent acting via modulation of the transcription factor NFkB and the Nrf2-Keap1 signaling pathway. In addition, a BRT-induced down-regulation of the immune checkpoint PD-L1 (programmed cell death ligand 1) expressed on cancer cells has been evidenced. Here we have performed a docking analysis of the direct binding of BRT to the PD-L1 protein, both in its monomeric and dimeric state. BRT appears to form stable complexes with PD-L1, with a preference for the dimeric form, binding at the interface of the two monomers. The calculated empirical energy of interaction (ΔE) value reaches -63.1 kcal/mol for the BRT-PD-L1 dimer complex, not far from the value calculated with the reference PD-L1 ligand BMS-202 (ΔE = -73.4 kcal/mol) under identical conditions. We also studied the potential PD-L1 dimer binding of 15 pseudoguaianolide sesquiterpene lactones analogues to BRT, including helenalin, gaillardin, bigelovin, coronopilin, and others. The docking analysis predicted that the SL chamissonolide (CHM) can also form equally stable complexes with PD-L1 dimer (ΔE = -64.8 kcal/mol). Preliminary compound structure-PD-L1 binding relationships have been delineated. This computational study supports the proposed interaction of BRT with PD-L1 and provides a guidance to the design of novel PD-L1 binders incorporating a SL-like tricyclic core unit.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"454-461"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39885647","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}

引用次数: 3

In silico screening for identification of fatty acid synthase inhibitors and evaluation of their antiproliferative activity using human cancer cell lines. 脂肪酸合酶抑制剂的筛选鉴定及其在人癌细胞系中的抗增殖活性评价。

IF 2.8

Journal of receptor and signal transduction research Pub Date : 2018-08-01 Epub Date: 2018-09-26 DOI: 10.1080/10799893.2018.1511730

Amrutha Nisthul A, Archana P Retnakumari, Shabna A, Ruby John Anto, C Sadasivan

{"title":"In silico screening for identification of fatty acid synthase inhibitors and evaluation of their antiproliferative activity using human cancer cell lines.","authors":"Amrutha Nisthul A, Archana P Retnakumari, Shabna A, Ruby John Anto, C Sadasivan","doi":"10.1080/10799893.2018.1511730","DOIUrl":"https://doi.org/10.1080/10799893.2018.1511730","url":null,"abstract":"De novo lipogenesis (DNL) by upregulation of fatty acid synthase (FASN) is an important metabolic alteration of cancer cells. FASN is over-expressed in several cancers and is often associated with a high risk of recurrence and poor prognosis. Differential expression of FASN in cancer cells and their normal counterparts leads to the impression that FASN can be an attractive druggable target in cancer therapy. Present study focuses on identification of inhibitors against FASN ketoacyl synthase (KS) domain from Asinex Biodesign compound database using in silico tools. Virtual screening resulted in the identification of two hit compounds BDD27845077 and BDD27845082 with a common core structure. Molecular Docking studies showed that BDD27845077 and BDD27845082 bind at the substrate entry channel of KS domain with GScore -12.03 kcal/mol and -12.29 kcal/mol respectively. Molecular dynamics (MD) simulation of the protein-ligand complexes shows the binding stability of ligands with FASN-KS. In vitro validation of BDD27845082 demonstrated that the compound possesses antiproliferative activity in a panel of human cancer cell lines including MDA-MB-231 (breast cancer), HCT-116 (colon cancer) and HeLa (cervical cancer) with maximum sensitivity against HCT-116 (IC 50 = 25 µM). The study put forward two lead compounds against FASN with favorable pharmacokinetic profile as indicated by virtual screening tools for the development of cancer chemotherapeutics.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"335-341"},"PeriodicalIF":2.8,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10799893.2018.1511730","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40544573","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}

引用次数: 10