The biphasic effect of soy isoflavones (genistein and daidzein) on oestrogen receptor (ER)α+ breast cancer cell proliferation is well documented, with concentrations of ≤10 µM promoting proliferation, and growth inhibitory and apoptotic effects seen at concentrations ≥10 µM. However genistein concentrations as low as 1nM may inhibit the proliferation of some ERα-/β+ cells. This is at odds with epidemiological evidence which suggests that high serum levels of soy isoflavones (around 1 µM) are associated with reduced breast cancer risk, particularly for ERα+ and premenopausal cancers. It is possible that interactions with endogenous oestrogens may be behind this discrepancy. The object here was to investigate combinations of genistein and daidzein at levels achievable in the serum through diet alone, at pre- and postmenopausal oestrogen levels, on breast cancer cell proliferation and apoptosis. ERα+ MCF7 and ERα-/β+ MDA-MB-231 cells were treated with genistein, daidzein and 17β-oestradiol at physiologically relevant levels. Physiological levels of soy isoflavones promoted but not inhibit the proliferation of MCF7 cells, whilst simultaneously inducing low level apoptosis. E2 acted synergistically on proliferation with the isoflavones, increasing proliferation further, but did not impact upon their apoptotic capacity. All concentrations of genistein and daidzein resulted in a slight reduction in MDA-MB-231 proliferation, with this dropping dramatically at the highest dose of 31.6 µM. Overall this suggests that physiological levels of isoflavones may be of benefit as chemotherapeutic agents against ERα-/β+ breast cancer. However they are not capable of reducing the proliferation of ERα+ MCF7 cells, or inhibiting oestrogenic promotion of growth. Other factors must be involved, not reflected by this model.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.