Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-]pyridine anticancer compound.

Tumor progression may be driven by a small subpopulation of cancer stem cells (CSCs characterized by CD44/CD24 phenotype). We investigated the influence of a newly developed thienopyridine anticancer compound (3-amino-5-oxo--naphthyl-5,6,7, 8-tetrahydrothieno[2,3-]quinoline-2-carboxamide, ) on the growth, survival and glycophenotype (CD15s and GM3 containing neuraminic acid substituted with acetyl residue, NeuAc) of breast and prostate cancer stem/progenitor-like cell population. MDA-MB-231 and Du-145 cells were incubated with compound alone or in combination with paclitaxel. The cellular metabolic activity was determined by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The type of cell death induced by 48-h treatment was assessed using a combination of Annexin-V-FITC and propidium iodide staining. Flow cytometric analysis was performed to detect the percentage of CD44/CD24 cells, and GM3 and CD15s positive CSCs, as well as the expression of GM3 and CD15s per one CSC, in both cell lines. Compound produces a dose- and time-dependent cytotoxicity, mediated mainly by apoptosis in breast cancer cells, and slightly (2.3%) but statistically significant lowering breast CSC subpopulation. GM3 expression per one breast CSC was increased, and the percentage of prostate GM3 CSC subpopulation was decreased in cells treated with compound compared with non-treated cells. The percentage of CD15s CSCs was lower in both cell lines after treatment with compound . Considering that triple-negative breast cancers are characterized by an increased percentage of breast CSCs and knowing their association with an increased risk of metastasis and mortality, compound is a potentially effective drug for triple-negative breast cancer treatment.