It has been demonstrated that ganoderma
acids suppress growth, angiogenesis and invasiveness of highly invasive and metastatic
breast cancer cells in vitro and vivo. However, the mechanism of action of ganoderma
acids in
breast cancer remains unknown. In the present study, we looked into the effect of
ganoderic acid Me (GA-Me) on cellular phenotypes and
tumor growth in the MDA-MB-231
breast cancer cell line. The results indicated the GA-Me inhibited
nuclear factor kappaB (NF-κB) activity at 24 h in MDA-MB-231 cells. When MDAMB- 231 cells were stimulated with
tumor necrosis factor-alpha (TNF-α), the inhibitory effects of GA-Me were still maintained. We demonstrated that GA-Me inhibited proliferation and invasion and induced apoptosis in MDA-MB-231 cells via suppressing the NF-κB activity. However, GA-Me did not inhibit the phosphorylation and degradation of IkappaB-α (IkB-α). GA-Me down-regulated the expression of various NF-κB-regulated genes including genes involved in cell proliferation (c-Myc and
cyclin D1), anti-apoptosis (Bcl-2), invasion (MMP-9) and angiogenesis (
VEGF,
interleukin (IL)-6 and -8). I.P. administration of GA-Me inhibited
tumor growth of MDA-MB-231 cells in vivo. Our results demonstrated that GA-Me inhibited proliferation, angiogenesis, invasion and induced apoptosis in MDA-MB-231 cells via suppressing NF-κB activity and the expression profile of its downstream genes. These findings provide evidence for a novel role of GA-Me in the prevention and treatment of
breast cancer by its ability to modulate the NF-κB signaling pathway.