Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Binding Pattern Elucidation of NNK and NNAL Cigarette Smoke Carcinogens with NER Pathway Enzymes: an Onco-Informatics Study

  • Jamal, Qazi Mohammad Sajid (Department of Health Information Management, College of Applied Medical Sciences, Buraydah Colleges, Al-Qassim-Buraydah King Abdulaziz Road, East Qassim University) ;
  • Dhasmana, Anupam (Environmental Carcinogenesis & Toxico-informatics Laboratory, Department of Biosciences and Bioengineering, Integral University) ;
  • Lohani, Mohtashim (Environmental Carcinogenesis & Toxico-informatics Laboratory, Department of Biosciences and Bioengineering, Integral University) ;
  • Firdaus, Sumbul (Environmental Carcinogenesis & Toxico-informatics Laboratory, Department of Biosciences and Bioengineering, Integral University) ;
  • Ansari, Md Yousuf (Pharmaco-informatics Department, National Institute of Pharmaceutical Education and Research (NIPER)) ;
  • Sahoo, Ganesh Chandra (Pharmaco-informatics Department, National Institute of Pharmaceutical Education and Research (NIPER)) ;
  • Haque, Shafiul (Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University)
  • Published : 2015.08.03
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Abstract

Cigarette smoke derivatives like NNK (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone) and NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol) are well-known carcinogens. We analyzed the interaction of enzymes involved in the NER (nucleotide excision repair) pathway with ligands (NNK and NNAL). Binding was characterized for the enzymes sharing equivalent or better interaction as compared to +Ve control. The highest obtained docking energy between NNK and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.13 kcal/mol, -7.27 kcal/mol, -8.05 kcal/mol and -7.58 kcal/mol respectively. Similarly the highest obtained docking energy between NNAL and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.46 kcal/mol, -7.94 kcal/mol, -7.83 kcal/mol and -7.67 kcal/mol respectively. In order to find out the effect of NNK and NNAL on enzymes involved in the NER pathway applying protein-protein interaction and protein-complex (i.e. enzymes docked with NNK/NNAL) interaction analysis. It was found that carcinogens are well capable to reduce the normal functioning of genes like RAD23A (HR23A), CCNH, CDK7 and CETN2. In silico analysis indicated loss of functions of these genes and their corresponding enzymes, which possibly might be a cause for alteration of DNA repair pathways leading to damage buildup and finally contributing to cancer formation.

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References

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