engleski

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

The emerging paradigm posits that tumor progression is driven by a small subpopulation of cancer stem cells (CSC characterized by CD44+/CD24- phenotype). We investigated the influence of a newly developed thienopyridine anticancer compound (3-amino-5-oxo-N-phenyl-5, 6, 7, 8- tetrahydrothieno[2, 3-b]quinoline-2-carboxamide, 1) on the growth, survival and glycophenotype (CD15s and GM3) of breast and prostate cancer stem/progenitor-like cell population. Breast triple-negative MDA-MB-231 and prostate Du-145 cancer cells were incubated with compound 1 alone, or in combination with paclitaxel. The cellular metabolic activity was determined by the MTT assay. The type of cell death induced by 48h treatment was assessed using combination of Annexin-V-FITC and propidium iodide staining. Additional flow cytometric analysis was performed to detect percentage of CD44+/CD24- cells, and GM3 and CD15s positive CSC, as well as the expression of GM3 and CD15s per one CSC, in both cell lines. Compound 1 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 1 compared to non-treated cells. The percentage of CD15s+ CSC was lower in both cell lines after treatment with compound 1. Considering that triple-negative breast cancers are characterized by an increased percentage of breast cancer stem cells and knowing their association with an increased risk of metastasis and mortality, 1 is a potentially effective drug for triple-negative breast cancer treatment.

breast ; prostate ; cancer stem cells ; GM3 ; CD15s

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