engleski

Novel Thieno [2,3-b]pyridine Anticancer Compound Lowers Cancer Stem Cell Fraction Inducing Shift of Lipid to Glucose Metabolism

(1) Background: Due to the role of cancer stem cells (CSCs) in tumor resistance and glycosphingolipid (GSL) involvement in tumor pathogenesis, we investigated the effect of a newly-synthesized compound (3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5, 6, 7, 8-tetrahydrothieno[2, 3-b]quinoline-2-carboxamide 1 on percentage of CSCs and the expression of six GSLs on CSCs and non-CSCs on breast cancer cell lines (MDA-MB-231 and MCF-7). We also investigat-ed the effect of 1 on the metabolic profile of these cell lines. (2) Methods: The MTT assay was used for cytotoxicity determination. Apoptosis and expression of GSLs was assessed by flow cytometry. A GC-MS-coupled system was used for separation and iden-tification of metabolites. (3) Results: Compound 1 was cytotoxic for both cell lines and the majority of cells died by treat-ment-induced apoptosis. The percentage of CSCs was significantly lower in the MDA-MB-231 cell line. Treatment with 1 caused a decrease of CSC IV6Neu5Ac-nLc4Cer+ MDA-MB-231 cells. In the MCF-7 cell line, the percentage of GalNAc-GM1b+ CSCs was increased, while the expression of Gg3Cer was decreased in both CSC and non-CSC. Twenty-one metabolites were identified by metabolic profiling. The major impact of the treatment was in glycolysis/gluconeogenesis, pyruvate and inositol metabolism. (4) Conclusion: Compound 1 exhibited higher potency in MBA-MB-231 cells, and it deserves further examination.

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

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