Long Term, Low Dose Genistein decreases Stem Cell Populations and Sensitizes Inflammatory Breast Cancer Cell Lines to Radiation

Abstract

Local recurrence in inflammatory breast cancer is common and is associated with poor
prognosis. Recurrence is driven by a small population of radioresistant breast cancer cells that
have stem-like properties. Previous studies have shown that high doses of the soy isoflavone
genistein have a growth inhibitory effect on tumor cells, and may sensitize non-inflammatory
breast cancer cells to radiation. The objective of this study was to determine the effect of
genistein on the growth and radioresistance of inflammatory breast cancer cells. We show that
short-term treatment of inflammatory cell lines IBC3 and SUM149 with genistein decreases
cell proliferation and mammosphere forming ability only at micromolar doses, but had minimal
effect on stem cell marker expression and radioresistance of these cells. However, long term
treatment with a low dose (nM) of genistein, which may mimic dietary intake, decreased stem
cell populations and mammosphere forming ability and increased radiation, induced cell death
in these lines. We propose that dietary intake of genistein may be associated with improved local
response to treatment in inflammatory breast cancer by decreasing growth of breast cancer
stem cells.