GM3 and CD15s highly expressing breast cancer stem cells are sensitive to novel thieno[2, 3- b]pyridine anticancer compound treatment

Small subpopulation of cancer stem cells (characterized by CD44+CD24− phenotype) expresses GM3(NeuAc) and CD15s glycoconjugates. Acidic glycosphingolipid GM3(NeuAc), containing neuraminic acid substituted with acetyl residue, is known to inhibit tyrosine kinase associated with fibroblast growth factor receptor. CD15s glycoconjugate is the major ligand of endothelial (E) selectin, responsible for cancer cell metastasizing. We performed preliminary studies of viability, and GM3(NeuAc) and CD15s expression after treatment of MDA-MB-231 triple-negative breast cancer cells with a newly developed thienopyridine anticancer compound (1). The MTT assay was used for the cellular metabolic activity determination. Cells expressing highly GM3(NeuAc) and CD15s were analysed for their CD44+CD24- subpopulation percentage, and GM3(NeuAc) and CD15s median fluorescence intensity in CD44+CD24- gate using flow cytometry. The percentages of highly expressing GM3(NeuAc) and CD15s cancer stem cells were lower, and their GM3(NeuAc) median fluorescence intensity was higher after treatment with compound 1 in comparison to non-treated cells. There was no difference in CD15s expression after treatment with the same compound. Knowing the inhibitory role of GM3(NeuAc) in fibroblast growth factor signal transduction, these findings render compound 1 potentially useful for triple- negative breast cancer treatment.