In-silico analysis of multi-pathway crosstalk inhibition of santamarin in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a highly prevalent disease worldwide, with 8.68% prevalence. However, present therapeutic measures are ineffective in coping with HCC due to significant therapy resistance. Therefore, crosstalk inhibition rather than targeting a single target is a more efficient strategy to reduce therapy resistance. In this study, we used computational methods to identify potential pathways involved in HCC and quantify their crosstalk. First, we evaluated the crosstalk between pathways from an HCC GEO dataset (GSE45267). 1526 genes were selected based on gene expression analysis, and 32 enriched pathways were identified based on 1526 genes. Then we predicted the effects of Santamarin on HCC by inhibiting individual and interlinked pathways, aiming to determine the maximum crosstalk inhibition. Santamarin has significantly inhibited crosstalk among six pathways, resulting in a reduction in network efficiency. Actually, CYP2C19 is a direct target of santamarin, which inhibits the pathway crosstalk among six pathways. Moreover, Santamarin has demonstrated substantial in vitro efficacy in destroying hepatic cancer cells. Overall, Santamarin has immense potential to inhibit crosstalk between primary pathways in HCC and could be considered as a future anticancer drug.