Matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) belong to a
zinc dependent family of
enzymes that degrade components of extracellular matrix. One postulated mechanism by which
inositol hexaphosphate (
phytic acid, IP6), an ubiquitous plant component, prevents the activation of
MMPs may be due to its ability to chelate minerals. The aim of the study was to evaluate the expression profile of MMP-2, MMP-9 and their tissue inhibitors
TIMP-1 and
TIMP-2 at the
mRNA level in human
colorectal cancer cell line Caco-2 treated with IP6. A kinetic study of MMP-2, MMP-9 and
TIMP-1,
TIMP-2 mRNAs was performed after cells treatment with 1; 2.5; 5 mM IP6 for 1, 6, 12 and 24 h. Quantification of genes expression was carried out using real time QRT-PCR technique. The gene encoding MMP-9 was neither constitutively expressed nor induced by IP6 in Caco-2 cells. IP6 at the concentration of 1 mM evoked increase in MMP-2 transcript level, however, its higher doses (2.5; 5 mM) caused a decrease in this gene expression at 1 h incubation. In 24 h lasting culture along with increasing IP6 concentration, the cells expressed lower and lower MMP-2
mRNA level. In response to 1 and 2.5 mM at 6 h, the cells demonstrated an increased transcriptional activity of the
TIMP-2 gene which was accompanied by a decrease in
TIMP-1 gene transcription. Treatment of cells with 2.5 mM IP6 at 12 h resulted in a strong increase in both
TIMP-1 and
TIMP-2 expression. The results of this study show that IP6 modulates MMP-2,
TIMP-1 and
TIMP-2 genes expression in
colon cancer cells at the transcriptional level in a way dependent on its concentration and time of interaction.