title: Ganoderic acid targeting nuclear factor erythroid 2-related factor 2 in lung cancer.
abstract: Lung cancer causes huge mortality worldwide, and targeting new pathway may provide an alternative in modulating signaling in cancer. Nuclear factor erythroid 2-related factor 2 is the major regulator of endogenous and exogenous stress by activating numerous antioxidant genes critical in cancer, Alzheimer's, Parkinson's, and inflammatory bowel diseases. Ganoderic acid is a triterpene from basiodiomycetes fungus Ganoderma lucidum with numerous therapeutic effects. In this study, ganoderic acid and its 50 isomers and natural activators were docked by receptor-based molecular docking using Maestro 9.6 (Schrödinger Inc.) in the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 signaling pathway. The receptor-based molecular docking reveals the best binding interaction of nuclear factor erythroid 2-related factor 2 and ganoderic acid A with GScore (-9.69) (kcal/mol), Lipophilic EvdW (-1.83), Electro (-0.72), Glide emodel (-73.369), H bond (-1.1), molecular mechanics/generalized Born surface area (-75.541) with Leu 718, Asp 800, Cys 797 residues involved in hydrogen bonding. The calculated docking energy highlights the lipophilic, hydrogen bonding, pi-pi stacking interactions, and non-covalent bonding. Analysis showed the involvement of cysteine and serine residues which were crucial in the activation and translocation from cytoplasm to the nucleus in the nuclear factor erythroid 2-related factor 2 signaling process. The molecular docking tool QikProp analyzed the absorption, distribution, metabolism, excretion, and toxicity but needs some modifications in their structure to satisfy Lipinski's rule. Ganoderic acid A is a best docked isoform which inhibits the cell proliferation, viability, migration, and reactive oxygen species and messenger RNA expression of nuclear factor erythroid 2-related factor 2 in H460 cells.
authors.affiliation: 1 Centre for Biosciences, Central University of Punjab, Bathinda, India.
authors.forename: Balraj Singh
authors.initials: BS
authors.lastname: Gill
authors.affiliation: 2 Centre for Plant Sciences, Central University of Punjab, Bathinda, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.affiliation: 3 Department of Biotechnology, Doaba College, Jalandhar, India.
authors.lastname: Navgeet
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003545:Cysteine / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D062105:Molecular Docking Simulation; D051267:NF-E2-Related Factor 2 / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation / Q000187:drug effects; D020033:Protein Isoforms / Q000737:chemistry* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D051267:NF-E2-Related Factor 2; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D014315:Triterpenes; C556862:ganoderic acid; D012694:Serine; D003545:Cysteine
keywords: Nuclear factor erythroid 2–related factor 2 signaling; antioxidant; cancer; ganoderic acid; molecular docking