Introduction: The existence of breast cancer stem-like cells (BCSCs) has profound implications for cancer\r\nprevention. Genistein, a predominant isoflavone found in soy products, has multiple robust anti-tumor effects in\r\nvarious cancers, especially in the breast and prostate cancer. In this study, we aimed to evaluate genistein inhibition\r\nof BCSCs and its potential mechanism by culturing MCF-7 breast cancer cells and implanting these cells into\r\nnude mice.\r\nMethods: Cell counting, colony formation and cell apoptosis analysis were used to evaluate the effect of genistein\r\non breast cancer cells� growth, proliferation and apoptosis. We then used mammosphere formation assay and\r\nCD44CD24 staining to evaluate the effect of genistein on BCSCs in vitro. A nude mice xenograft model was\r\nemployed to determine whether genistein could target BCSCs in vivo, as assessed by real-time polymerase chain\r\nreaction (PCR) and immunohistochemical staining. The potential mechanism was investigated utilizing real-time\r\nPCR, western blotting analysis and immunohistochemical staining.\r\nResults: Genistein inhibited the MCF-7 breast cancer cells� growth and proliferation and promoted apoptosis. Both\r\nin vitro and in vivo genistein decreased breast cancer stem cells, and inhibited breast cancer stem-like cells through\r\ndown-regulation of the Hedgehog-Gli1 Signaling Pathway.\r\nConclusions: We demonstrated for the first time that genistein inhibits BCSCs by down-regulating Hedgehog-Gli1\r\nsignaling pathway. These findings provide support and rationale for investigating the clinical application of\r\ngenistein in treating breast cancer, and specifically by targeting breast cancer stem cells.
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