Keele Research Repository
Explore the Repository
Pervan, M, Marijan, S, Markotić, A, Pilkington, LI, Haverkate, NA, Barker, D, Reynisson, J, Meić, L, Radan, M and Čikeš Čulić, V (2022) Novel Thieno [2,3-b]pyridine Anticancer Compound Lowers Cancer Stem Cell Fraction Inducing Shift of Lipid to Glucose Metabolism. International Journal of Molecular Sciences, 23 (19).
Novel Thieno [2,3-ibi]pyridine Anticancer Compound Lowers Cancer Stem Cell Fraction Inducing Shift of Lipid to Glucose Metab.pdf - Published Version
Available under License Creative Commons Attribution.
Download (4MB) | Preview
Abstract
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 the 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 investigated the effect of 1 on the metabolic profile of these cell lines. The MTT assay was used for cytotoxicity determination. Apoptosis and expression of GSLs were assessed by flow cytometry. A GC-MS-coupled system was used for the separation and identification of metabolites. Compound 1 was cytotoxic for both cell lines, and the majority of cells died by treatment-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. Compound 1 exhibited higher potency in MBA-MB-231 cells, and it deserves further examination.
Item Type: | Article |
---|---|
Additional Information: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Uncontrolled Keywords: | breast cancer cells; cancer stem cells; newly synthesized thieno [2,3-b]pyridine compound; glycosphingolipids; metabolomics |
Subjects: | Q Science > Q Science (General) |
Divisions: | Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering |
Related URLs: | |
Depositing User: | Symplectic |
Date Deposited: | 31 Oct 2022 17:24 |
Last Modified: | 31 Oct 2022 17:24 |
URI: | https://eprints.keele.ac.uk/id/eprint/11652 |