7-3--dihydroxy-4--methoxyisoflavone and 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.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Caspase 3; Caspase 8; Cell Line, Tumor; Cell Proliferation; Estrogen Receptor alpha; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Isoflavones; JNK Mitogen-Activated Protein Kinases; Male; Mice; Mice, Nude; Mitogen-Activated Protein Kinase 14; Mitogen-Activated Protein Kinase 3; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Protein Interaction Mapping; Proto-Oncogene Mas; Receptor-Interacting Protein Serine-Threonine Kinases; Signal Transduction; Tumor Burden; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays

The incidence of nasopharyngeal carcinoma (NPC) in China is relatively higher than that throughout the rest of the world, and NPC is geographically distributed. Long non-coding RNA (lncRNA) plays a key role in the development of tumors. Recent studies have found that the lncRNA Ewing sarcoma-associated transcript 1 (EWSAT1) is highly expressed in various tumors and also in NPCs. The isoflavone calycosin, which is a typical Chinese herbal medicine, can inhibit the growth of breast cancer, colorectal cancer, osteosarcoma and other cancers. The aim of our study was to select NPCs that were sensitive to calycosin and whether calycosin had an effect on NPC cells. If it does, are the effects related to a high expression of EWSAT1? We also verified that EWSAT1 was highly expressed in NPC cells. At the same time, we found that calycosin inhibited the growth of NPC cell lines. To further determine whether the effect of calycosin on NPC cells was related to EWSAT1, we used NPC cells with different concentrations of calycosin and found that the expression of EWSAT1 decreased significantly with increasing concentrations of calycosin and that the expression of downstream factors and pathways were also affected. It was demonstrated that calycosin affected NPC cell growth by regulating EWSAT1 and its downstream pathway. In addition, we overexpressed EWSAT1 and found that the increased expression of EWSAT1 weakened the growth inhibitory effect of calycosin on NPC cells.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins; Isoflavones; Mice; Nasopharyngeal Carcinoma; RNA, Long Noncoding; Signal Transduction; Time Factors; TNF Receptor-Associated Factor 6; Tumor Burden; Xenograft Model Antitumor Assays