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Borrelidin has limited anti‐cancer effects in bcl‐2 overexpressing breast cancer and leukemia cells and reveals toxicity in non‐malignant breast epithelial cells
Author(s) -
Gafiuc Diana,
Weiß Marlene,
Mylonas Ioannis,
Brüning Ansgar
Publication year - 2014
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2946
Subject(s) - cytotoxicity , cancer research , cytotoxic t cell , leukemia , cancer cell , jurkat cells , cell culture , cancer , breast cancer , medicine , immunology , biology , in vitro , biochemistry , t cell , immune system , genetics
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. Copyright © 2013 John Wiley & Sons, Ltd.