STUDI KEMOPREVENTIF SAFRON (Crocus sativus) TERHADAP KANKER LAMBUNG BERBASIS IN SILICO NETWORK PHARMACOLOGY (Pendekatan in silico)

Background : Gastric cancer is a heterogeneous hereditary cancer with multifactorial causes including genetic and environmental factors and is the fourth leading cause of cancer death in the world.
Objective : to obtain data and pharmacological mechanisms of Crocus sativus compounds that have the potential to have chemopreventive activity and data on target proteins that play an important role in the gastric cancer signaling pathway.
Methods : Crocus sativus metabolite compounds were collected from the KNApSAcK database. Crocus sativus metabolite targets were collected using SwissTarget Prediction while gastric cancer using GeneCard. Intersection of Crocus sativus metabolite target data and gastric cancer using VennyTools was downloaded, included with GeneCard and PPI network construction was made with STRING. Intersection data were constructed into a protein target-metabolite compound interaction network with STITCH. Network visualization using Cytoscape.
Results : Based on the STITCH prediction results at a confidence level of 0.40, myricetin compounds interact with target proteins EGFR, GSK3β, ABCC1, PIK3CG, PARP1 and TOP2A and quercetin interacts with target proteins ABCC1, CDK2, EGFR, GSK3B, GTSP1, ESR1, JUN, MAPK8, PARP1, PIK3CG, PTGS2, SRC and TOP2A. Myricetin is predicted to inhibit ABCC1 and PIK3CG, downregulate EGFR to target the PI3K/Akt pathway and also induce GSK-3β dephosphorylation through inhibition of PAK1 protein expression. Quercetin is predicted to inhibit ABCC1, CDK2, GSK3B, GTSP1, JUN, MAPK, PARP1 and PIK3CG and activate EGFR target proteins. Quercetin can activate FOXO1 and block EGFR/Akt activation. Knockdown of FOXO1 decreased quercetin-mediated FasL and p21 expression, followed by increased apoptosis and G2 cell cycle arrest. Overexpression of JUN plays an important role in various biological functions such as apoptosis, proliferation, invasion, and migration.