Abstract
Xanthohumol is a unique prenylated flavonoid in hops (Humulus lupulus L.) and beer. Xanthohumol has been shown to possess a variety of pharmacological activities. There is little research on its effect on doxorubicin-resistant breast cancer cells (MCF-7/ADR) and the cancer stem-like cells exiting in this cell line. In the present study, we investigate the effect of xanthohumol on the viability and stemness of MCF-7/ADR cells. Xanthohumol inhibits viability, induces apoptosis, and arrests the cell cycle of MCF-7/ADR cells in a dose-dependent manner; in addition, xanthohumol sensitizes the inhibition effect of doxorubicin on MCF-7/ADR cells. Interestingly, we also find that xanthohumol can reduce the stemness of MCF-7/ADR cells evidenced by the xanthohumol-induced decrease in the colony formation, the migration, the percentage of side population cells, the sphere formation, and the down-regulation of stemness-related biomarkers. These results demonstrate that xanthohumol is a promising compound targeting the doxorubicin resistant breast cancer cells and regulating their stemness, which, therefore, will be applied as a potential candidate for the development of a doxorubicin-resistant breast cancer agent and combination therapy of breast cancer.
Highlights
Breast cancer is a common malignant tumor in woman worldwide
We revealed the sensitivity of MCF-7/ADR cells to XN and the potent synergy effect effect of XN when combined with DOX
Chemotherapy, we revealed that XN could down-regulate the cancer stemness characters in could down-regulate the cancer stemness characters in MCF-7/ADR cells, for the first time
Summary
Breast cancer is a common malignant tumor in woman worldwide. Chemotherapy using doxorubicin (DOX) and docetaxel is still one of the clinically effective treatment strategies for breast cancer. The efficacy of DOX is limited by its side effects and the drug resistance, which is the major reason for the failure of breast cancer treatment [1]. The cancer stem-like cells are more resistant to standard chemotherapy drugs [2] and contribute significantly to the drug resistance. Breast cancer stem-like cells are a small population of mostly resting cells defined by their long life, high clonogenicity, self-replicating potential, plasticity, and drug resistance [3]. Novel strategies are needed to overcome the drug resistance and chemical therapies targeting the breast cancer stem-like cells may contribute a novel method [2]. Plant-derived compounds and their derivatives [4,5]
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