Xanthohumol inhibits cellular proliferation in a breast cancer cell line (MDA-MB231) through an intrinsic mitochondrial-dependent pathway

AIMS: Xanthohumol isolated from hops has been reported to exhibit anticancer effects in diverse human cancers. However, its effect on breast cancer has not yet been clearly defined. The purpose of this study was to investigate the effects of xanthohumol on breast cancer cell proliferation. MATERIALS AND METHODS: After treatment with 5 mu M, 10 mu M, and 20 mu M xanthohumol for 48 h, cells from the human breast cancer cell line MDA-MB-231 were studied using colony assay, flow cytometry, and western blotting. RESULTS: The survival rate of the MDA-MB231 cells treated with 10 mu M and 20 mu M xanthohumol for 48 h decreased significantly by 64.7 +/- 1.8% and 40.1 +/- 1.8%, respectively. The numbers of SubG0/G1 cells in the group treated with 10 mu M and 20 mu M xanthohumol increased significantly to 11.3 +/- 0.2 and 18.4 +/- 0.1, respectively. A ladder pattern of DNA fragmentation was also observed. Xanthohumol increased the expression of Bax in the mitochondria, which correspondingly decreased in the cytoplasm. The activity of caspase-3 and caspase-9 was shown to increase significantly in the treated groups but not in the control group. CONCLUSIONS: Xanthohumol inhibited the proliferation of MDA-MB-231 cells through a mitochondria- and caspase-dependent apoptotic pathway. This result suggests that xanthohumol might serve as a novel therapeutic drug for breast cancer.