Marijan, S, Markotić, A, Mastelić, A, Režić-Mužinić, N, Pilkington, LI, Reynisson, J ORCID: https://orcid.org/0000-0003-4174-9512 and Čulić, VČ (2020) Glycosphingolipid expression at breast cancer stem cells after novel thieno[2,3-b]pyridine anticancer compound treatment. Scientific Reports, 10 (1). 11876 - ?.

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Abstract

Glycosphingolipid expression differs between human breast cancer stem cells (CSC) and cancer non-stem cells (non-CSC). We performed studies of viability, type of cell death, cancer stem cell percent and glycosphingolipid expression on CSC and non-CSC after treatment of MDA-MB-231 and MDA-MB-453 triple-negative breast cancer cells with a newly developed thienopyridine anticancer compound (3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, 1). Compound 1 was cytotoxic for both breast cancer cell lines and the majority of cells died by treatment-induced apoptosis. The percent of cancer stem cells and number of formed mammospheres was significantly lower. Glycosphingolipids IV6Neu5Ac-nLc4Cer and GalNAc-GM1b (IV3Neu5Ac-Gg5Cer) not reported previously, were identified in both CSCs and non-CSCs. IV6Neu5Ac-nLc4Cer had increased expression in both CSCs and non-CSCs of both cell lines after the treatment with 1, while GM3 (II3Neu5Ac-LacCer) had increased expression only on both cell subpopulations in MDA-MB-231 cell line. GalNAc-GM1b, Gb4Cer (GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1Cer) and GM2 (II3Neu5Ac-GalNAcβ1-4Galβ1-4Glcβ1-1Cer) were increased only in CSCs of both cell lines while GD3 was decreased in CSC of MDA-MB-231 cell line. Due to its effect in reducing the percentage of cancer stem cells and number of mammospheres, and its influence upon several glycosphingolipid expressions, it can be concluded that compound 1 deserves attention as a potential new drug for triple-negative breast cancer therapy.

Item Type: Article
Additional Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Uncontrolled Keywords: Drug development, Molecular medicine
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Related URLs:
Depositing User: Symplectic
Date Deposited: 14 Aug 2020 14:56
Last Modified: 14 Aug 2020 14:56
URI: https://eprints.keele.ac.uk/id/eprint/8550

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