Ivermectin as an inhibitor of cancer stem­like cells.

The aim of the present study was to demonstrate that ivermectin preferentially inhibited cancer stem­like cells (CSC) in breast cancer cells and downregulated the expression of 'stemness' genes. Computational searching of DrugBank, a database of approved drugs, was performed using the principles of two­dimensional similarity searching; the chemical structure of salinomycin was used as a query. Growth inhibition of the breast cancer cell lin e MDA­MB­231 by ivermectin was investigated in the total cell population, in cell spheroids and in sorted cells that expressed cluster of differentiation (CD)44+/CD24­. The effects of ivermectin treatment on the expression of pluripotency and self­renewal transcription factors, such as homeobox protein nanog (nanog), octamer­binding protein 4 (oct­4) and SRY­box 2 (sox­2), were evaluated by reverse transcription­quantitative polymerase chain reaction and western blotting. Ivermectin exhibited a similarity value of 0.78 in reference to salinomycin. Ivermectin demonstrated an inhibitory effect upon the growth of MDA­MB­231 cells in the range of 0.2­8 µM. Ivermectin preferentially inhibits the viability of CSC­enriched populations (CD44+/CD24­ and cells growing in spheroids) compared with the total cell population. The opposite pattern was observed with paclitaxel treatment. Ivermectin exposure reduced the expression of nanog, oct­4 and sox­2 at the mRNA and protein levels. Ivermectin preferentially inhibited the CSC subpopulation in the MDA­MB­231 cells and downregulated the expression of genes involved in the maintenance of pluripotency and self­renewal.