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Journal of Applied Life Sciences International, 2394-1103,Vol.: 19, Issue.: 2

Original-research-article

Uncovering the Selective Drug Targets in Urethane-Mediated Lung Cancer through Network Approach

 

Toluwase Hezekiah Fatoki1*, Subhajit Dutta2 and Abiodun Samuel Oyedele1,3

1Department of Biochemistry, Federal University of Technology, PMB 704 Akure, Nigeria.

2Cancer Genetics and Vasculature Research Group, School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, Odisha-752050, India.

3Department of Chemistry, Tennessee State University, Nashville, TN 37209-1561, USA.

Article Information

Editor(s):

(1) Adisorn Ratanaphan, Associate Professor, Pharmaceutical Biotechnology,  Faculty of Pharmaceutical Sciences, Prince of Songkla University, Thailand.

Reviewers:

(1) Tariq Namad, HMIMV, Rabat, Morocco.

(2) Neema Tiwari, India.

(3) Dago Dougba Noel, UPGC-University, Republic of Cote d'Ivoire.

Complete Peer review History: http://www.sciencedomain.org/review-history/27649

Abstracts

Aim: To identify the driver targets associated with urethane mediated tumorigenesis by pharmacokinetics prediction, target prediction and gene expression network analysis.

Methodology: Standard bioinformatics tools were used, which include SwissADME, SwissTargetPrediction, eXpression2Kinases (X2K), and ClustalO.

Results: It was found that urethane has very low lipophilicity and high gastrointestinal absorption. Urethane major probable targets include tyrosyl-DNA phosphodiesterase 1 (TDP1), acetyl cholinesterase and muscarinic acetylcholine receptors. Enrichment analysis showed that transcription factors most expressed through urethane-targeted genes include TRIM28, RELA, SUZ12 and EGR1 while protein-protein interaction analysis showed that these transcription factors were mostly coordinated by heat shock protein 90 (Hsp90) isoforms (HSP90AA1, HSPAB1 and HSP90B1). The implicated targets were highly associated with cyclin-dependent kinases (CDKs) and mitogen-activated protein kinases (MAPKs).

Conclusion: Selective inhibition of TDP1 and Hsp90 isoforms and not transcription factors, could be the central therapeutic point for suppression and prevention of lung tumour.

Keywords :

Cancer; tumorigenesis; urethane; ethyl carbamate; TDP1; Hsp90; gene network.

Full Article - PDF    Page 1-12

DOI : 10.9734/JALSI/2018/45097

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