4-(Methylthio)butyl isothiocyanate inhibits the proliferation of breast cancer cells with different receptor status

Background: Epidemiological studies indicate that the consumption of Brassicaceae plants, a rich source of biologically active isothiocyanates (ITCs), may effectively reduce cancer risk. In the current study, we evaluated the anticancer potential of 4-(methylthio) butyl ITC (erucin, ERN) against three phenotypically different breast cancer cell lines: MDA-MB-231, SKBR-3 and T47D. Methods: The effect of ERN on the viability of breast cancer cells was evaluated using sulforhodamine B and clonogenic assays, and acridine orange/ethidium bromide staining. Cell cycle was investigated using flow cytometry. The status of signaling molecules was examined by western blot analysis. Results: ERN decreased the viability of all tested cancer cell lines in a concentration-dependent manner; this effect was much weaker in normal breast cells (MCF-10A). ERN induced cell cycle arrest in the G2/M phase, down-regulated the phosphorylation of S6 ribosomal protein in all tested breast cancer cell lines, and reduced HER2 receptor levels in SKBR-3 cells. A 24-h treatment with lower concentrations of ERN (5-20 mM) induced apoptosis; higher ERN concentrations (40 mM) induced necrosis. The latter also irreversibly inhibited the proliferative potential of cancer cells. Conclusion: ERN effectively inhibits proliferation of breast cancer cells irrespectively of their receptor status. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.