title: Ganoderic Acid A Targeting β-Catenin in Wnt Signaling Pathway: In Silico and In Vitro Study.
abstract: Wnt signaling pathways are the group of signaling transduction controlling the embryonic development, cell proliferation, cell migration, cell fate specification, and body axis pattern. Nuclear accumulation of β-catenin in Wnt signaling is a widely recognized marker of poor cancer prognosis which regulates fat and glucose metabolism. Ganoderic acid is a triterpene isolated from fungus Ganoderma lucidum renowned for its pharmacological effects. The present study revealed the mechanistic study of β-catenin with 50 isoforms of ganoderic acid by molecular docking using Maestro 9.6 (Schrödinger Inc) in Wnt signaling pathway. Molecular docking reveals the binding interaction of β-catenin and ganoderic acid A with GScore (-9.44), kcal/mol, lipophilic EvdW (-2.86), electro (-0.72), Glide emodel (-50.401), MM-GBSA (-87.441), H bond (-1.91) with Lys 180 and Asn 220 residues involved in hydrogen bonding. Qikprop analyzed the absorption, distribution, metabolism, excretion, and toxicity and confirmed that most of the isoforms satisfies Lipinski rule but needs little modifications in their structure. The ganoderic acid A is the best-docked isoforms which inhibits the proliferation, viability, and intracellular ROS of pancreatic cancer RIN-5F cells in a dose-dependent manner.
authors.affiliation: Centre for Biosciences, Central University of Punjab, Bathinda, 151001, India.
authors.forename: Balraj Singh
authors.initials: BS
authors.lastname: Gill
authors.affiliation: Centre for Biosciences, Central University of Punjab, Bathinda, 151001, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Biotechnology, HMV College, Jalandhar, India. geet20capricorn@gmail.com.
authors.lastname: Navgeet
mesh_terms: D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D005453:Fluorescence; D006538:Heptanoic Acids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008024:Ligands; D020033:Protein Isoforms / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D006538:Heptanoic Acids; D008024:Ligands; D020033:Protein Isoforms; D051176:beta Catenin; D007810:Lanosterol; C515005:ganoderic acid A
keywords: Diabetes II; Ganoderic acid; Molecular docking; Wnt signaling; β-catenin