BIOINFORMATIC STUDY ON EFFECT OF XANTHOHUMOL AS BIOACTIVE COMPOUND OF HOP IN THE INHIBITION OF THE MAPK/ERK PATHWAY IN THYROID CANCER

Background: Xanthohumol is one of the main bioactive compounds extracted from the female flowers of the hops plant (Humulus lupulus L), that has been shown in several studies to have anti-cancer effects.The MAPK/ERK pathway is one of the key pathways in the regulation of gene expression, cell growth and survival. The abnormal activation of this pathway leads to the uncontrolled cell proliferation in thyroid cancer. This study aims to perform a bioinformatic screening of the proteins in the MAPK/ERK pathway and introduce them as target protein to Xanthohumol. In addition, due to the significant role of EGFR, Grb2, SOS proteins in the MAPK/ERK pathway, they have also been studied. Method: Using SwissADME software, first the physicochemical, pharmacokinetic and pharmacodynamic characteristics of Xanthohumol are predicted. Then three-dimensional structure of Xanthohumol and target proteins (EGFR, Grb2, SOS, RAS, BRAF, MEK1, MEK2, ERK1, ERK2) were collected from PubChem database and Protein Data Bank, finally, using Auto Dock 4.1.the molecular docking were studied. Results: Our study shows lack of cytotoxicity in Xanthohumol. In addition, Xanthohumol with proper physicochemical properties does not induce drug resistance through pump P-glycoprotein mechanism. Analysis of molecular docking indicate that Xanthohumol has inhibitory potential to the all proteins studied. Note that its strongest interaction is with MEK2 protein with binding energy-7.04kcal.mol-1. Conclusion: According to our results, Xanthohumol has inhibitory potential to the all proteins present in the MAPK/ERK pathway. It lacks cytotoxicity. Thus, it can be considered as an alternative inhibitor for the MAPK/ERK pathway in thyroid cancer cells.