PMID- 32449282 OWN - NLM STAT- MEDLINE DCOM- 20210827 LR - 20211204 IS - 1872-8081 (Electronic) IS - 0951-6433 (Linking) VI - 46 IP - 4 DP - 2020 Jul TI - Anticancer targets and mechanisms of calycosin to treat nasopharyngeal carcinoma. PG - 675-684 LID - 10.1002/biof.1639 [doi] AB - 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. CI - (c) 2020 International Union of Biochemistry and Molecular Biology. FAU - Liu, Fangxian AU - Liu F AD - Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China. FAU - Pan, Qijin AU - Pan Q AD - Department of Oncology, Guigang City Peoples' Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi, China. FAU - Wang, Liangliang AU - Wang L AD - Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China. FAU - Yi, Shijiang AU - Yi S AD - Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China. FAU - Liu, Peng AU - Liu P AD - Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China. FAU - Huang, Wenjun AU - Huang W AUID- ORCID: 0000-0002-4094-7843 AD - Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi, China. LA - eng GR - 20190218-5-11/Guilin Scientific Research and Technology Development Plan Project/ GR - Z20190615/Scientific research project for self-financing of Guangxi Medicine and Health/ PT - Journal Article DEP - 20200524 PL - Netherlands TA - Biofactors JT - BioFactors (Oxford, England) JID - 8807441 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (ESR1 protein, human) RN - 0 (Estrogen Receptor alpha) RN - 0 (Isoflavones) RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - 09N3E8P7TA (7,3'-dihydroxy-4'-methoxyisoflavone) RN - EC 2.7.11.1 (RIPK1 protein, human) RN - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (MAPK3 protein, human) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (CASP8 protein, human) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspase 8) SB - IM MH - Animals MH - Antineoplastic Agents, Phytogenic/*pharmacology MH - Apoptosis/drug effects/genetics MH - Caspase 3/genetics/metabolism MH - Caspase 8/genetics/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Estrogen Receptor alpha/genetics/metabolism MH - *Gene Expression Regulation, Neoplastic MH - *Gene Regulatory Networks MH - Humans MH - Isoflavones/*pharmacology MH - JNK Mitogen-Activated Protein Kinases/genetics/metabolism MH - Male MH - Mice MH - Mice, Nude MH - Mitogen-Activated Protein Kinase 14/genetics/metabolism MH - Mitogen-Activated Protein Kinase 3/genetics/metabolism MH - Nasopharyngeal Carcinoma/*drug therapy/genetics/metabolism/pathology MH - Nasopharyngeal Neoplasms/*drug therapy/genetics/metabolism/pathology MH - Protein Interaction Mapping MH - Proto-Oncogene Mas MH - Receptor-Interacting Protein Serine-Threonine Kinases/genetics/metabolism MH - Signal Transduction MH - Tumor Burden/drug effects MH - Tumor Suppressor Protein p53/genetics/metabolism MH - Xenograft Model Antitumor Assays OTO - NOTNLM OT - calycosin OT - mechanism OT - nasopharyngeal carcinoma OT - network pharmacology OT - targets EDAT- 2020/05/26 06:00 MHDA- 2021/08/28 06:00 CRDT- 2020/05/26 06:00 PHST- 2020/03/06 00:00 [received] PHST- 2020/04/19 00:00 [revised] PHST- 2020/04/28 00:00 [accepted] PHST- 2020/05/26 06:00 [pubmed] PHST- 2021/08/28 06:00 [medline] PHST- 2020/05/26 06:00 [entrez] AID - 10.1002/biof.1639 [doi] PST - ppublish SO - Biofactors. 2020 Jul;46(4):675-684. doi: 10.1002/biof.1639. Epub 2020 May 24.