Preliminary studies have shown that genistein modulates the expression of some heat shock proteins in mammary tumor cells. In this study, we investigated the effect of genistein pretreatment on the expression of glucose-regulated protein 78 (GRP78) in both estrogen receptor-positive (MCF-7) and -negative (MDA-MB-231) cells. Genistein increased the expression of GRP78 in a dose- and time-dependent manner and suppressed glucose uptake in both cell lines. However, induction of GRP78 by genistein appears not to be directly associated with inhibition of glucose uptake. Genistein treatment also made MDA-MB-231 cells more sensitive to doxorubicin, probably via increased GRP78 expression, but had no effect or even decreased drug sensitivity in MCF-7 cells. These results suggest that genistein may be exploited as an enhancer of chemotherapeutic agents in certain types of breast cancer.
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