Carvacrol suppressed LIHC via SLC6A3

Abstract

BackgroundLiver hepatocellular carcinoma (LIHC) is the second leading cause of tumor-related death in the world and its study is urgent. Carvacrol was also found to inhibit multiple cancer types. Here we proposed that carvacrol inhibited LIHC.MethodsWe used MTT assay to determine the inhibition of carvacrol on LIHC cells. BATMAN-TCM was used to predict targets of carvacrol. These targets were further screened by their survival association and expression in cancer using TCGA data. The bioinformatic screened candidates were further validated in in-vitro experiments and clinical samples. Finally, docking models of the interaction of carvacrol and target protein were conducted.ResultsCarvacrol inhibited the viability of LIHC cell lines. 40 target genes of carvacrol were predicted, 8 of them associated with survival. 4 genes were found differentially expressed in LIHC vs. normal liver. Among these genes, the expression of SLC6A3 and SCN4A were found affected by carvacrol in LIHC cells, but only SLC6A3 correlated with the viability inhibition of carvacrol on LIHC cell lines. 5 docking models of the interaction of carvacrol and SLC6A3 were established with one that had a good binding affinity. SLC6A3 knockdown and expression revealed that SLC6A3 promoted the viability of LIHC cells.ConclusionCarvacrol inhibited the viability of LIHC cells by downregulating SLC6A3.