Structurally related lanostane-type triterpenes, ganoderic acid A, F and H (GA-A, GA-F, Ganoderic acid H), were identified in an oriental medicinal mushroom Ganoderma lucidum. METHODS AND RESULTS: In the present study we evaluated the effect of GA-A, Ganoderic acid H and GA-F on highly invasive human breast cancer cells. We showed that GA-A and Ganoderic acid H suppressed growth (cell proliferation and colony formation) and invasive behavior (adhesion, migration and invasion) of MDA-MB-231 cells. Our results suggest that GA-A and Ganoderic acid H mediate their biological effects through the inhibition of transcription factors AP-1 and NF-kappaB, resulting in the down-regulation of expression of Cdk4 and the suppression of secretion of uPA, respectively. Furthermore, the activity of ganoderic acids is linked to the hydroxylation in the position 7 and 15 (GA-A) and 3 (Ganoderic acid H) in their triterpene lanostane structure. CONCLUSIONS: In conclusion, hydroxylated triterpenes from G. lucidum could be promising natural agents for the therapy of invasive breast cancers. |