Broussoflavonol B restricts growth of ER-negative breast cancer stem-like cells.

Abstract

Accumulating experimental and clinical evidence has indicated that tumor-initiating or cancer stem-like cells are a sub-population of tumor cells capable of initiating and driving tumor growth, and cancer stem-like cells are resistant to most current cancer therapies, including chemo- and radiation therapy. More effective targeted-therapeutic approaches are urgently needed to eliminate cancer stem-like cells. Here, we report that broussoflavonol B, a chemical purified from the bark of the Paper Mulberry tree (broussonetia papyrifera), exhibited potent growth inhibitory activity towards estrogen receptor (ER)-negative breast cancer SK-BR-3 cells at sub-micromolar concentrations. Broussoflavonol B more potently inhibited growth and induced differentiation of stem-like SK-BR-3 cells-compared to the anti-estrogen tamoxifen. In addition, broussoflavonol B treatment also reduced the steady, state levels of the Human epidermal growth factor receptor-2 (HER2) and ER-α36, a variant of ER-α. Our results, thus, indicate that broussoflavonol B is a potent growth inhibitor of ER-negative breast cancer stem-like cells and provide a rationale for pre-clinical and clinical evaluation of broussoflavonol B for breast cancer therapy.