Ganoderic acid targeting multiple receptors in cancer: in silico and in vitro study.
Receptor tyrosine kinases (RTKs) are transmembrane high-affinity surface receptors responsible for cell migration, adhesion, apoptosis, metabolism, and cell proliferation activities in various cancers. Minute aberration in the RTK signaling modulates the downstream signaling pathways that results in cancer. Ganoderic acid is a triterpene isolated from Ganoderma lucidum, which is renowned for its therapeutics effect, especially in cancer. The present study discusses receptor-based molecular docking of insulin receptor (IR), insulin-like growth factor receptor 1 (IGFR-1), vascular endothelial growth factor receptor-1 (VEGFR-1), vascular endothelial growth factor receptor-2 (VEGFR-2), and estrogen receptor (ER) with 50 isoforms of ganoderic acid along with natural inhibitors. These receptors were assessed for toxicity (ADMET) by using Maestro 9.6 (Schrödinger Inc). The calculated docking free energy yielded an excellent dock score for the ganoderic acid when docked with proteins IR, IGFR-1, VEGFR-1, VEGFR-2, and ER, suggesting its potential in combating cancer. Protein-ligand profile highlighted the binding interactions comprising lipophilic, hydrogen bonding, pi-pi stacking interactions, and noncovalent bonding which play a pivotal role in targeting cancer. In silico studies revealed structure of ganoderic acid A as best isoforms among 50 isoforms which exhibits biological activity in liver cancer cells. Ganoderic acids A significantly decrease the viability, proliferation, and oxidative stress in a dose-dependent manner in liver cancer cells.
Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151001, India.
Balraj Singh
BS
Gill
Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151001, India.
Navgeet
Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151001, India. sanjeevpuchd@gmail.com.|Centre for Plant Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151001, India. sanjeevpuchd@gmail.com.
Sanjeev
S
Kumar
D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D003198:Computer Simulation; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D017526:Receptor, IGF Type 1 / Q000737:chemistry / Q000378:metabolism; D011972:Receptor, Insulin / Q000737:chemistry / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000737:chemistry / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000737:chemistry / Q000378:metabolism
D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D014315:Triterpenes; C556862:ganoderic acid; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
Cancer; Ganoderic acid; Molecular docking; Oxidative stress; Receptor tyrosine kinase