Bufalin, a key active ingredient of the Chinese medicine Chan Su, inhibits breast cancer tumorigenesis in vitro and in vivo. Here, we found that the pan-caspase inhibitor zVAD-fmk failed to inhibit bufalin-induced cell death in MCF-7 and MDA-MB-231 human breast cancer cells, confirming that the cell death induced by bufalin is caspase-independent. Instead, bufalin increased the expression of the necroptosis mediators RIP1 and RIP3. Bufalin-induced cell death was prevented by small molecule inhibitors of RIP1 and poly (ADP-ribose) polymerase-1 (PARP-1) or genetic knockdown of RIP3 by shRNA transfection. In addition, ectopic RIP3 expression enhanced cell death by bufalin. We also found that bufalin increased intracellular reactive oxygen species levels; and cell death by bufalin was inhibited by the antioxidant NAC. In a mouse xenograft model of human breast cancer, bufalin induced PARP-1-dependent tumor cell death and inhibited tumor growth. These results demonstrated that bufalin inhibits human breast cancer tumorigenesis by inducing cell death through the reactive oxygen species-mediated RIP1/RIP3/PARP-1 pathways.
Abstract. The aim of the current study was to investigate the effects of resveratrol (Res) on vascular endothelial growth factor (VEGF) expression and cell proliferation in the human osteosarcoma cell line U20S. U20S cells were treated with Res at various concentrations (0, 10, 20 and 40 µmol/l) for various times (24, 48 and 72 h). The inhibitory effect of Res on U20S proliferation was observed using methyl thiazolyl tetrazolium (MTT) colorimetry. VEGF expression was determined using real-time polymerase chain reaction (RT-PCR) and western blot analysis. The inhibitory effect of Res on U20S proliferation increased as the concentration of Res increased. The inhibitory effect also increased with time. Res had an inhibitory effect on VEGF expression and significantly inhibited U20S cell proliferation. Res may exert an anti-osteosarcoma effect by inhibiting VEGF expression in tumor cells.
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