Anticancer targets and mechanisms of calycosin to treat nasopharyngeal carcinoma.

Calycosin is a naturally occurring phytoestrogen, and it has the anti-nasopharyngeal carcinoma (NPC) action played by calycosin. However, the elaborate mechanisms of calycosin treating NPC remain to be unrevealed. In current report, a promising tool of network pharmacology method was used to uncover the anti-NPC targets and therapeutic mechanisms played by calycosin. Furthermore, were conducted to validate the bioinformatic findings in human and preclinical studies. As results, the bioinformatic findings showed the core anti-NPC targets played by calycosin included tumor protein p53 (TP53), mitogen-activated protein kinase 14 (MAPK14), caspase 8 (CASP8), mitogen-activated protein kinase 3 (MAPK3), caspase 3 (CASP3), receptor interacting protein kinase 1 (RIPK1), proto-oncogene c (JUN), and estrogen receptor 1 (ESR1). Concurrently, the top 20 biological processes and top 20 pharmacological pathways of calycosin treating NPC were identified and illustrated. In clinical data, NPC samples showed up-regulated expression of MAPK14, reduced TP53, and CASP8 expressions in comparison with those in non-NPC controls. As revealed in experimental data, calycosin-treated NPC cells resulted in reduced cell survival rate, increased cell apoptosis. In apoptosis-specific staining, calycosin-treated NPC cells exhibited elevated apoptotic cell number. Following the immunostaining assays, the results indicated increased TP53-, CASP8-positive cells, and reduced MAPK14-positive cells in calycosin-treated NPC cells and xenograft tumor sections. Altogether, the bioinformatic findings from network pharmacology reveal all core targets and mechanisms of calycosin treating NPC, and some of bioinformatic findings are identified using human and preclinical experiments. Notably, the screened biotargets may be potentially used to clinically treat NPC.