Ceramides have been proposed as potential therapeutic strategy with regard to their ability to induce cell death. We previously demonstrated that
C2-ceramide generated apoptosis in bronchocarcinoma BZR cells. We here investigated whether
ceramides also target other molecules involved in cell-cell or cell-matrix interactions during
cancer progression. A SuperArray(R) analysis showed that
ceramides modulate gene expression after 2 h. Among deregulated genes, we observed an inhibition of the transcript coding for the pro-metastatic
enzyme MMP-2. The pharmacological inhibitor of
caspases cascade,
ZVAD-fmk, did not prevent C2-ceramide-induced down-regulation of MMP-2 ruling out apoptosis as a mediator of this event, whereas inhibition of oxidative stress using NAC confirmed a role for ROS. This effect of
C2-ceramide was associated with changes in
histone H3 acetylation. However, although
histone deacetylase inhibitors are also currently under investigation for their anti-
tumor activity, we demonstrated here that a combined treatment with
trichostatin A abrogated both MMP-2 down-regulation and reduced invasive properties elicited by
C2-ceramide alone. Hence, this study demonstrates that besides its apoptotic effect,
C2-ceramide also exhibits anti-invasive properties, showing a dual beneficial effect against
cancer progression, but casts some doubt on the use of
HDAC inhibitors as combined treatment with drugs that trigger the
ceramide pathway.