Ganoderic acids suppress growth and angiogenesis by modulating the NF-kappaB signaling pathway in breast cancer cells
Menée sur une lignée cellulaire de cancer du sein, cette étude montre que l'acide ganodérique inhibe la croissance tumorale et l'angiogenèse en régulant la voie de signalisation NF-kappaB
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-kappaB) activity at 24 h in MDA-MB-231 cells. When MDAMB- 231 cells were stimulated with tumor necrosis factor-alpha (TNF-alpha), 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-kappaB activity. However, GA-Me did not inhibit the phosphorylation and degradation of IkappaB-alpha (IkB-alpha). GA-Me down-regulated the expression of various NF-kappaB-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-kappaB 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-kappaB signaling pathway.
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