The molecular mechanism of xanthohumol‐induced apoptosis in MCF‐7 and MCF‐7/ADR cells

Abstract

Xanthohumol, the principal prenylated chalcone that only found in the hop plant, Humulus lupulus L., has been shown to possess a variety of pharmacological activities. In the present study, we examined the xanthohumol induced apoptotic effects in breast cancer cells using wild‐type breast cancer cell (MCF‐7) and adriamycin resistant breast cancer cells (MCF‐7/ADR). Xanthohumol inhibited cell viability and induced apoptosis of both MCF‐7 and MCF‐7/ADR cells in a dose dependent manner. Interestingly, MCF‐7/ADR cells were more susceptible against xanthohumol than the wild‐type MCF‐7 cells as determined by MTT assay and PI staining. We found increased phosphorylation of STAT‐3 in MCF‐7/ADR cells which on xanthohumol treatment completely inhibited. Furthermore, MCF‐7/ADR cells were more sensitive to AG 1024, a selective inhibitor of IGF‐IR. The effect of xanthohumol on STAT‐3 inhibition was similar to that of AG 1024. In the down‐stream of STAT‐3, xanthohumol increased proapoptotic Bax and decreased antiapoptotic Bcl‐2 in MCF‐7, whereas xanthohumol decreased antiapoptotic Bcl‐x/L in MCF‐7/ADR. In case of caspase activity, xanthohumol induced cleavage of caspase‐9, ‐3 and ‐7 in MCF‐7/ADR cells and cleaved caspase‐9 in MCF‐7 cells. The apoptosis‐inducing activity of xanthohumol may be different depending on the cell type, especially in relation to STAT‐3 expression level.