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

Abstract

Short CommunicationPage 60 ABSTRACTLocal 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.

Mechanistic evaluation of phytochemicals in breast cancer remedy: current understanding and future perspectives

“… 111 Long-term low-dose genistein administration sensitized inflammatory breast cancer cell lines to radiation and reduced mammosphere formation and the growth of stem cell populations. 112 Downregulation of Hedgehog–Gli1 signalling by genistein is also linked with reduced bCSCs. 113 …”

Unifying Mechanism for Nutrients as Anticancer Agents: Electron Transfer, Reactive Oxygen Species and Oxidative Stress

“…Long term, low dose genistein consumption decreases stem cell population and sensitizes inflammatory breast cancer cell lines to radiation (Sims-Moutada, Opdenaker, Davis, & Wu, 2015). A report deals with genistein as a dietary phytochemical target in human prostate cancer stem cells (Zhang, Li, Jiao et al, 2012).…”