Genistein inhibits the proliferation of human HER2-positive cancer cells by downregulating HER2 receptor

Background: It was well studied that HER2/ErbB2/p185 overexpression in human malignant cancers correlates with poor prognosis and chemo-resistance. Meanwhile, Genistein (4,5,7trihydroxyisoflavone), a major isoflavone component of soybeans and other leguminous plants, has been shown to exhibit a potent anti-proliferative effect on some sex hormone dependent cancers. Objective: The effects of genistein on the proliferation of human HER2-overexpressing breast and ovarian cancer cell lines were investigated, and the action mechanism was explored. Methods: Western blotting, fluorescence-activated cell sorting (FACS) and immunofluorescence methods, cell proliferation assay kit from Promega and cell apoptosis assay kit from Biolegend were used. The doseor time-response relationship of genistein were observed on the HER2negative breast cancer cell line MCF-7 or HER2-positive breast cancer cell lines BT-474 and MCF-7/Her2 derived from MCF-7, and ovarian cancer cell line SKOV-3. Results: The addition of genistein ranged from 1-10g/ml in the medium for 48 hours had a marked inhibition on the proliferation of HER2-positive cancer cell lines MCF-7/Her2, BT-474 and SKOV-3, compared with tamoxifen and DMSO control (P<0.01), and a dose-dependent response was presented. However, genistein exerted a weak inhibitive effect on HER2-negative breast cancer cell line MCF-7. There was a significant apoptosis or necrosis effect of BT-474 cells induced by 10 g/ml genistein for 12-48 hours in comparison with DMSO control (P<0.01), and a time-dependent response relationship. Moreover, genistein could down-regulate HER2 receptor expression and AKT kinase activity by using immunofluorescence and western blotting methods. Functional Foods in Health and Disease 2013; 3(7):291-299 Page 292 of 299 Conclusion: Our findings demonstrated that genistein could effectively inhibit the proliferation of HER2-positive cancer cell lines, which should be through down-regulating HER2 receptor and downstream signaling.