engleski

GC-MS based comparative analysis of MDA-MB-231 AND MCF- 7 cancer cells treated with novel thieno[2,3- b]pyridine derivative

Metabolic profiling of cancer cells has ever growing role in elucidation of molecular base of cancer development, progression and prognosis. In this study, we investigated the effect of a novel thieno[2, 3-b]pyridine derivative on the metabolic profile of two breast cancer lines with different hormonal status ; MDA-MB-231 (triple negative) and MCF-7 (ER, PR, HER2-). The thieno[2, 3-b]pyridines were initially discovered as potential inhibitors of phospholipase C (PLC) isoforms by virtual high throughput screen (vHTS). GC-MS coupled system was used for separation and identification of metabolites. The objective was to identify the compound effect on each metabolite and to find metabolites significantly different between treated and control cells in each line. Data processing, data normalization, statistical analysis and high-level functional interpretation was performed using MetaboAnlayst, a webbased platform for comprehensive analysis of quantitative metabolomics data. Test of statistical significance shows that results for MDA-MB-231 cells are more significant than for MCF-7 cells. PCA results show that drug treatment causes metabolic alternations in both cell lines. Quantitative enrichment analysis was employed to identify patterns of metabolite concentrations and to help elucidate possible biological mechanisms. The results of analysis reveal that treatment has a major impact in glucose/energy metabolism specifically in glycolysis/gluconeogenesis, pyruvate metabolism, Warburg effect, inositol metabolism for both lines. Metabolic profiling of cancer cells plays an increasingly important role for research on the mechanism of action of anticancer drug candidates.

breast cancer cells ; cancer stem cells ; newly synthesized thieno [2, 3-b]pyridine compound ; glycosphingolipids ; metabolomics

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