Drug screening and biomarker gene investigation in cancer therapy through the human transcriptional regulatory network

He, Zihao; Gao, Kai; Li, Dong; Liu, Liu; Qu, Xinchi; Zou, Zhengkai; Wu, Yang; Bu, Dechao; Guo, Jincheng; Zhao, Yi

doi:10.1016/j.csbj.2023.02.005

Cited by 10 publications

(4 citation statements)

References 85 publications

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“…As recognized documented antiproliferative mechanism for cyanopyridine‐based compounds is EGFR inhibition, according to a review of the literature. [ 32,47–49 ] Accordingly, the three most effective cyanopyridin‐2‐one sulfonamides, 6e , 6k , and 6l , were assessed for their potential EGFR inhibitory action to examine the tested compounds’ molecular‐level ability to suppress cellular growth. With IC 50 of 95.1, 113.0, and 104.2 nM, respectively, the three tested cyanopyridines ( 6e , 6k , and 6l ) showed intriguingly effective inhibition of EGFR at the nanomolar range as shown in Supporting Information: Figure .…”

Section: Resultsmentioning

confidence: 99%

“…As recognized documented antiproliferative mechanism for cyanopyridine-based compounds is EGFR inhibition, according to a review of the literature. [32,[47][48][49] Accordingly, the three most (Table 2). This indicates that the cyanopyridin-2-one sulfonamides described herein exert their antiproliferative effect by inhibiting EGFR, which causes cell death.…”

Section: Ca and Egfr Inhibition Assaysmentioning

confidence: 99%

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Identification of 3‐(5‐cyano‐6‐oxo‐pyridin‐2‐yl)benzenesulfonamides as novel anticancer agents endowed with EGFR inhibitory activity

Shaldam,

Khalil,

Almahli

et al. 2023

Archiv der Pharmazie

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New 5‐cyano‐6‐oxo‐pyridine‐based sulfonamides (6a–m and 8a–d) were designed and synthesized to potentially inhibit both the epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA), with anticancer properties. First, the in vitro anticancer activity of each target substance was tested using Henrietta Lacks cancer cell line and M.D. anderson metastasis breast cancer cell line cells. Then, the possible CA inhibition against the human CA isoforms I, II, and IX was investigated, together with the EGFR inhibitory activity, with the most powerful derivatives. The neighboring methoxy group may have had a steric effect on the target sulfonamides, which prevented them from effectively inhibiting the CA isoforms while effectively inhibiting the EGFR. The effects of the 5‐cyanopyridine derivatives 6e and 6l on cell‐cycle disruption and the apoptotic potential were then investigated. To investigate the binding mechanism and stability of the target molecules, thorough molecular modeling assessments, including docking and dynamic simulation, were performed.

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Section: Resultsmentioning

confidence: 99%

Section: Ca and Egfr Inhibition Assaysmentioning

confidence: 99%

Identification of 3‐(5‐cyano‐6‐oxo‐pyridin‐2‐yl)benzenesulfonamides as novel anticancer agents endowed with EGFR inhibitory activity

Shaldam,

Khalil,

Almahli

et al. 2023

Archiv der Pharmazie

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“…[ 19 ] Resveratrol was known to enhance the expression of miR-200b and miR-34a, which are typical miRNAs that inhibit the growth and metastasis of lung cancer cells. [ 20 ] In addition, resveratrol lowered miR-21, which role as an oncogene. [ 19 21 ] The importance of EGFR was also highlighted as the main receptor that regulates cancer proliferation in lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Exploring the anticancer potential of Eleutherine bulbosa: A systematic network pharmacology study on lung cancer

Mutiah,

Rachmawati

2024

Journal of Advanced Pharmaceutical Technology &Amp; Research

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Chemotherapy application in lung cancer patients has several side effects and shows lower effectiveness due to chemoresistance. Although Eleutherine bulbosa (Mill.) Urb. (EBE) elicit anticancer properties, yet the exact profile of its active compounds and lung cancer inhibition mechanisms were not fully understood. This study aimed to identify suggestive compounds from EBE extract and explain the molecular mechanisms of EBE against lung cancer. Identification of the compound from the EBE extract was confirmed using liquid chromatography–tandem mass spectrophotometry (LC–MS/MS). The bioavailability profile of three major metabolites was identified using absorption, distribution, metabolism, excretion, toxicity software. The anticancer molecular mechanism prediction of the drugs was ascertained by network pharmacology using Cytoscape 3.9.1 and the protein–protein interaction network technique with STRING 11.0. Interaction between resveratrol and extracellular growth factor receptor (EGFR) was analyzed using site-specific molecular docking with erlotinib as the control using PyRx Autodock Vina 9.0 and BIOVIA Discovery Studio. A total of 16 active compounds were identified from LC-MS/MS. Only resveratrol showed anticancer properties by its interaction with 13 genes and 6 signaling pathways related to lung cancer. The molecular docking result supports the network pharmacology finding. The binding affinity of resveratrol with EGFR, important receptor in lung cancer, was more negative (−6.9 kcal/mol) than erlotinib (−6.2 kcal/mol) as the control. Evidence suggested that resveratrol in EBE exhibits anticancer effects by modulating lung cancer cell proliferation and apoptosis through EGFR binding.

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“…Variations in an individual's genome can affect drug metabolism, absorption, distribution, and excretion, thereby affecting drug efficacy and adverse effects [15]. Therefore, knowing an individual's drug-disease genetic information can help doctors better choose drugs and drug dosages to improve treatment efficacy and reduce the risk of adverse reactions.…”

Section: Introductionmentioning

confidence: 99%

New perspectives on the potential of tetrandrine in the treatment of non-small cell lung cancer: bioinformatics, Mendelian randomization study and experimental investigation

Luo,

Mo,

et al. 2024

Aging

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Background: Although there are numerous treatment methods for NSCLC, long-term survival remains a challenge for patients. The objective of this study is to investigate the role and causal relationship between the target of tetrandrine and non-small cell lung cancer (NSCLC) through transcriptome and single-cell sequencing data, summary-data-based Mendelian Randomization (SMR) and basic experiments. The aim is to provide a new perspective for the treatment of NSCLC. Methods: We obtained the drug target gene of tetrandrine through the drug database, and then used the GSE19188 data set to obtain the NSCLC pathogenic gene, established a drug-disease gene interaction network, screened out the hub drug-disease gene, and performed bioinformatics and tumor cell immune infiltration analysis. Single-cell sequencing data (GSE148071) to determine gene location, SMR to clarify causality and drug experiment verification. Results: 10 drug-disease genes were obtained from 213 drug targets and 529 disease genes. DO/GO/KEGG analysis showed that the above genes were all related to the progression and invasion of NSCLC. Four drugdisease genes were identified from a drug-disease PPI network. These four genes were highly expressed in tumors and positively correlated with plasma cells, T cells, and macrophages. Subsequent single-cell sequencing data confirmed that these four genes were distributed in epithelial cells, and SMR analysis revealed the causal relationship between CCNA2 and CCNB1 and the development of NSCLC. The final molecular docking and drug experiments showed that CCNA2 and CCNB1 are key targets for tetrandrine in the treatment of NSCLC.

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Drug screening and biomarker gene investigation in cancer therapy through the human transcriptional regulatory network

Cited by 10 publications

References 85 publications

Identification of 3‐(5‐cyano‐6‐oxo‐pyridin‐2‐yl)benzenesulfonamides as novel anticancer agents endowed with EGFR inhibitory activity

Identification of 3‐(5‐cyano‐6‐oxo‐pyridin‐2‐yl)benzenesulfonamides as novel anticancer agents endowed with EGFR inhibitory activity

Exploring the anticancer potential of Eleutherine bulbosa: A systematic network pharmacology study on lung cancer

New perspectives on the potential of tetrandrine in the treatment of non-small cell lung cancer: bioinformatics, Mendelian randomization study and experimental investigation

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