In silico analysis and experimental validation to exhibit anti-nasopharyngeal carcinoma effects of plumbagin, an anti-cancer compound.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is publicly known as a malignant tumor. Our previous study reported that plumbagin exhibits potent anti-cancer actions. Nevertheless, more mechanical details of plumbagin against NPC remain unknown. The present study aimed to unmask the core targets/genes and anti-NPC mechanisms involved in the signaling pathways of plumbagin prior to biochemical validation. METHODS: A network pharmacology approach was employed to respective identification of mutual and core targets/genes in plumbagin and/treating NPC. Molecular docking determination was used to identify core target proteins for biochemical validation using human and cell line samples. RESULTS: In total, 60 anti-NPC genes of plumbagin were screened out, and then nine core target genes of plumbagin against NPC were identified accordingly. The enrichment findings revealed detailed biological functions and pharmacological pathways of plumbagin against NPC. Moreover, in silico analysis using molecular docking had determined the core targets for further experimental validation, comprising protein kinase B (AKT1) and sarcoma gene (SRC). In human sample validation, clinical NPC sections showed increased positive expression of AKT1 and SRC. Additionally, plumbagin-treated NPC cells resulted in inactivated protein expression of AKT1 and SRC. CONCLUSION: The re-identified core targets/genes in the molecular docking report may function as plumbagin-related pharmacological targets for treating NPC via experimental validation. Furthermore, additional anti-NPC molecular mechanisms of plumbagin action were disclosed on the basis of enrichment findings. © 2022 Society of Chemical Industry.

Anti-neoplastic characteristics and potential targets of calycosin against bisphenol A-related osteosarcoma: bioinformatics analysis.

Environmentally, bisphenol A (BPA) is a well-known pollutant caused human health risk, including osteosarcoma (OS). OS, a deadly bone neoplasia, may occur in children and adults. However, the anti-OS pharmacotherapy prescribes limitedly in clinical practice. Interestingly, previous experimental evidences indicate calycosin-exerting potential anti-OS actions. Thus, in this report, we aimed to further characterize and detail the therapeutic targets and molecular mechanisms of calycosin-anti-BPA-related OS by using network pharmacology and molecular docking analyses. In results, the bioinformatics data disclosed all mapped, core targets, biological functions, molecular pathways of calycosin to treat BPA-related OS. The computational analysis using molecular docking indicated that potential binding ability of core targets in calycosin to treat BPA-related OS was identified. Moreover, detailed biological functions and optimal pathways of calycosin-anti-BPA-related OS were revealed, as shown in integrated network maps. Taken together, these network pharmacology and structural biology findings illustrate the core biotargets, pharmacological functions and pathways of calycosin-anti-BPA-related OS. Potentially, these core targets identified by molecular docking may attribute to the potential clinical application of calycosin against BPA-related OS.[Formula: see text].

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.

The Effects of Plumbagin on Pancreatic Cancer: A Mechanistic Network Pharmacology Approach.

BACKGROUND This study aimed to use a network pharmacology approach to establish the effects of plumbagin on pancreatic cancer (PC) and to predict core targets and biological functions, pathways, and mechanisms of action. MATERIAL AND METHODS Genes associated with the pathogenesis of PC were obtained from a database of gene-disease associations (DisGeNET). Putative genes associated with plumbagin were identified from the databases of drug target identification (PharmMapper), target prediction of bioactive components (SwissTargetPrediction), and comprehensive drug target information (DrugBank). PC targets of plumbagin were harvested by using a functional enrichment analysis tool (FunRich). The data of function-related protein-protein interactions (PPIs) with a confidence score >0.9 were obtained by using functional protein association networks (STRING). The network interactions of plumbagin and PC targets and function-related proteins were constructed through complex network analysis and visualization (Cytoscape). The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis were used to identify the effects of plumbagin. RESULTS The most important biotargets for plumbagin in PC were identified as TP53, MAPK1, BCL2, and IL6. A total of 1,731 annotations and 121 enriched pathways for plumbagin and PC were identified by KEGG and GO analysis. The top 10 signaling pathways of plumbagin and PC were screened, followed by identification of biological components and functions. CONCLUSIONS Network pharmacology established the effects of plumbagin on PC, predicted core targets, biological functions, pathways, and mechanisms of action. Further studies are needed to validate these predictive biotargets in PC.

Clinical immunophenotype of nasopharyngeal neuroendocrine carcinoma with metastatic liver cancer.

BACKGROUND: Nasopharyngeal neuroendocrine carcinoma (NNC) refers to a rare and lethal cancer, characterized with high risk of metastases. Here, we report a case of nasopharyngeal neuroendocrine carcinoma with subsequent liver metastases to discuss its clinical immunophenotype and challenges. METHODS: In clinical biochemical assays, hematological determination, immunohistochemical examination, imaging medicine investigations, and therapeutical analysis were subjected to the hospitalized patient, respectively. RESULTS: A group of clinical detectable data highlighted that clinical immunophenotype of nasopharyngeal neuroendocrine carcinoma was identified in immunohistochemical inspection, followed by validation of liver metastases via imaging observations. Subsequent chemotherapy schedule showed disease remission in certain aspect before patient' death. CONCLUSION: Our current clinical data disclose that it is vital to identify nasopharyngeal neuroendocrine carcinoma for main cause of liver metastases with potential risk. Further, early diagnosis and effective pharmacotherapy may improve the survival rate of NNC patient with liver metastases.

Clinical biocharacterization of immunophenotype in hepatocellular carcinoma patients.

In current observations, we investigated the clinical immunophenotypes in liver cells to assess the metastasic predisposition in advance hepatocellular carcinoma patients. In method, we harvested the clinically diagnosed data from 8 liver cancer subjects. Definitely, all patients were received standard chemotherapeutics when being confirmed as advanced liver cancer via clinical diagnosis. In parallel, biopsy liver samples were subjected to histopathological and immunoblotting assays. Representatively, clinical laboratory results showed that blood parameters resulted in notable elevations of aminotransferases (ALT, AST), hepatitis B e antibody (HBeAb), alpha-fetoprotein (APF) and carcinoembryonic antigen (CEA). In addition, immunoassays exhibited significant hepatocellular expressions of Ki-67 (cell proliferation), CD34 (angiogenesis), as well as strong production of CK8, CK10 (metastasis) in liver cells, as revealed in both the immunostaining and Western blotting analyses. Collectively, the present clinical findings elucidate that the metastasis of hepatocellular carcinoma relates to unregulated cell proliferation and angiogenesis. In particular, current representative immunophenotypes may be served as potential biomarkers for screening metastasis of advanced liver cancer.

Clinical characterization for proliferation and metastasis in advanced hepatocellular carcinoma patients.

Here we reported that association between drug resistance and carcinomatosis in advanced liver cancer cases. All subjects (n=4) were periodically received chemotherapeutic agents when clinical manifestation being defined serologically. Hepatic specimen was harvested via biopsy and further prepared as paraffin-slice before conducting immunohistochemistry. As a consequence, more detectable biomarkers, such as AST, AFP, GGT2, were high expressed in plasma when compared to clinical standards. DNA topoisomerase II (TOPO II), Ki-67 were immunoreactively labeled in cytoplasm/membrane and nucleolus of liver cancer cells, while hepatocellular tumor protein p53 was negative or non-detected. Additionally, we found that hepatobiliary cancer showed epithelial differentiation with pronounced CK19 immunoreactivity when metastasizing. Our clinicopathologic findings demonstrate that correlation between carcinomatous proliferation/metastasis and drug resistance protein expression. Furthermore, these evidences indicate that TOPO II may be a biomarker for advanced hepatocellular carcinoma patient receiving chemotherapeutics.