Eremurus spectabilis, Rich Source of Isoorientin: Isolation, Quantification and Anti-Cancer Activity on SH-SY5Y Neuroblastoma Cells
CURRENT PHARMACEUTICAL ANALYSIS
Authors: Karaoglan, Esen Sezen; Gundogdu, Gulsah; Secme, Mucahit; Senol, Onur; Miloglu, Fatma Demirkaya; Dodurga, Yavuz; Tufekci, Ali Riza
Abstract
Background: Eremurus spectabilis BIEB. (Liliaceae) is an edible and medicinal plant in Turkey. Introduction: This study was designed to isolate and quantify isoorientin in leaves of E. spectabilis and exhibit its effect on SH-SY5Y neuroblastoma cell line. Methods: Purity and identification of isoorientin were evaluated by 1D-NMR, 2D-NMR and Q-TOF were isolated from E. spectabilis via column chromatography. An HPLC method was also developed and validated for isoorientin. Results: Quantitative measurements indicated that contents of isoorientin in E. spectabilis leaves were 81.01 mg/g and MeOH extract were 23.75 mg/gr. All measurements were performed at 350 nm. Anti-cancer activity was investigated on cell culture. IC50 doses of isoorientin were detected as 250 mu M at the 48th hour in SH-SY5Y cells by XTT assay. Real-time PCR analysis in SH-SY5Y cells showed that CCND1, CDK6, casp-9, Bax, ATR, Bcl-2, CHEK1 and CHEK2, expressions significantly reduced in experimental group when compared with the control group. p53, p21, caspase-3, caspase-8, Bcl-2, ATM and ERCC1 expressions increased in the experimental group when compared with the control group (P<0.05). Conclusion: Measurements revealed that E. spectabilis contains high amount of isoorientin and can be used as a new source of this compound. In addition to this, isoorientin affects cell proliferation of neuroblastoma cells by cell cycle control and apoptosis gene expression and it could be used as a therapeutic agent, however, more studies must be performed to clarify its mechanism.
Comprehensive transcriptomic analysis identifies novel regulators of lung adenocarcinoma
JOURNAL OF CELL COMMUNICATION AND SIGNALING
Authors: Mokhlesi, Amir; Talkhabi, Mahmood
Abstract
Lung adenocarcinoma (LA) is a subtype of lung cancer that accounts for about 40% of all lung cancers. Analysis of molecular mechanisms controlling this cancer can help scientists to detect, control and treat LA. Here, a microarray dataset (GSE118370) containing six normal lung (NL) and six LA samples was screened using GEO2R to find differentially expressed genes (DEGs). Then, DAVID, KEGG and ChEA were used to analyze DEGs-related gene ontology, pathways and transcription factors (TFs), respectively. The Protein-protein interaction network for DEGs and TFs was constructed by STRING and Cytoscape. To find microRNAs and metabolites associated with DEGs, miRTarBase and HMDB were used, respectively. It was found that 350 genes were upregulated and 608 genes were downregulated in LA. The upregulated genes or LA-related gens were enriched in biological process and pathways such as extracellular matrix disassembly and p53 signaling pathway, whereas the downregulated genes or NL-related genes were enriched in cell adhesion and cell-surface receptor signaling pathway. ESR1, KIF18B, BIRC5, CHEK1, CCNB1 and AURKA were determined as hub genes for LA. FOXA1 and TFAP2A had the highest number of connectivity in LA-related TFs. hsa-miR-192-5p and hsa-miR-215-5p could target the highest number of LA-related genes. Metabolite analysis showed that Estrone and NADPH were among the top ten metabolites associated with LA-related genes. Taken together, LA-related genes, especially the hub genes, TFs, and metabolites might be used as novel markers for LA, as well as for diagnosis and guiding therapeutic strategies of LA.