Lx2-32c inhibits the formation of mammosphere from MDA-MB-231 cells and induces apoptosis involving in down-regulating FoxM1.

Cancer stem cells (CSCs) are a subset of cancer cells which have self-renewal ability and exist in various tumors. Inhibition of CSCs self-renewal is considered as a new method for tumor therapy. A novel semi-synthetic taxane analogue, Lx2-32c, could overcome drug resistance in various cancer cell lines. In this study, it was found that Lx2-32c inhibited the proliferation and mammosphere formation of MDA-MB-231-derived cancer stem cell-like cells (MCSCLCs) and induced apoptosis, as well as down-regulated the expression of FoxM1 and CD44 in MCSCLCs. Simultaneously, it was proved that Lx2-32c combined with thiostreption, a FoxM1 inhibitor inhibited proliferation and mammosphere formation of MCSCLCs and induced apoptosis to a more extent than Lx2-32c alone; thiostreption could also enhance the effect of Lx2-32c of reduction of the expression of FoxM1 and CD44. All of these results indicated that Lx2-32c is a novel semi-synthetic taxane analogue which inhibits the self-renewal of MCSCLCs cells and induces apoptosis involving in down-regulating FoxM1.