Cancer metastasis represents the most important cause of cancer death and agents 
that may inhibit tumor cell invasion have been extensively pursued. In the 
present study, we have examined the anti-invasive effect of apicidin 
[cyclo(N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl -L-2-amin 
o-8-oxodecanoyl)], a fungal metabolite that was identified as an antiprotozoal 
agent known to inhibit parasite histone deacetylase (HDAC). We show that 
apicidin significantly inhibits H-ras-induced invasive phenotype of MCF10A human 
breast epithelial cells in parallel with a specific downregulation of matrix 
metalloproteinase (MMP)-2, but not MMP-9. We also show that apicidin induces a 
morphological reversal and growth inhibition of H-ras MCF10A cells similar to 
that induced by other HDAC inhibitors. Taken in conjunction with the fact that 
uncontrolled ras activation is probably the most common genetic defect in human 
cancer cells, our data showing the anti-invasive and detransforming activities 
of apicidin in H-ras-transformed MCF10A cells may suggest a potential use of 
HDAC inhibitors for treatment of cancer.