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.
Highlights
Glycosphingolipid expression differs between human breast cancer stem cells (CSC) and cancer non-stem cells
We described glycoconjugate GM3 and CD15s expression in MDA-MB-231 triple negative breast cancer stem cell subpopulation cultured with 3-amino-5-oxo-N-naphthyl5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, which was developed as a putative phospholipase C (PLC) inhibitor
In the MDA-MB-231 cell line Compound 1 was shown to be cytotoxic in 0.5 μM concentration after only 4 h of treatment and ten times lower concentration (50 nM) resulted in cytotoxicity after 48 h
Summary
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]quinoline2-carboxamide, 1). We described glycoconjugate GM3 and CD15s expression in MDA-MB-231 triple negative breast cancer stem cell subpopulation cultured with 3-amino-5-oxo-N-naphthyl5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, which was developed as a putative PLC inhibitor. A close structural analogue of 3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, or compound 12 was chosen for this study due to its enhanced potency against the MDAMB-231 cell line and its mechanism of action has been investigated[3,4] Due to their ability to self-renew and to regenerate the primary tumour phenotypic heterogeneity, cancer stem cells are important therapeutical targets[5]. In addition to this canonical lethal CSClike MDA-MB-231, non-stem breast cancer MDA-MB-453 c ells[22] were studied in their response to new inhibitor
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
