Clinically effective anti-
cancer drugs have to tread a narrow line between selective cytotoxicity on
tumor cells and tolerable adverse effects against healthy tissues. This causes the failure of many potential
cancer drugs in advanced clinical trials, hence signifying the importance of a comprehensive initial estimate of the cytotoxicity of prospective anti-
cancer drugs in preclinical studies. In this study, the cytotoxicity of
borrelidin, a
macrolide antibiotic with a high cytotoxic selectivity for proliferating endothelial cells and
leukemia cells, was tested on malignant and non-malignant breast cells. Highly metastatic
breast cancer cell lines (MDA-MB-231 and MDA-MB-435) showed promising results and exhibited good sensitivity to
borrelidin at low nanomolar concentrations, but
borrelidin was cytotoxic to a non-malignant breast epithelial cell line (MCF10A) as well. Furthermore, although a high sensitivity of endothelial cells (human umbilical vein endothelial cells; HUVEC) and individual
leukemia cell lines (Jurkat and IM9) to
borrelidin was confirmed in this study, another
leukemia cell line (HL60) and an immortalized endothelial cell line (EA.hy926) displayed a significantly decreased sensitivity. Reduced sensitivity to
borrelidin was associated with elevated bcl-2 expression in these cell lines. In conclusion, the results presented show that
borrelidin displays high and selective cytotoxicity against subgroups of
cancer cells and endothelial cells, but, owing to its non-specific toxicity to non-malignant cells, its clinical application might be restricted because of likely adverse effects and limited efficacy in bcl2-overexpressing
cancer cells.