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The influence of inositol hexaphosphate on the expression of genes encoding matrix metalloproteinases 2 and 9 and their tissue inhibitors in human colon cancer cells

Małgorzata Kapral ,  Joanna M. Wawszczyk ,  Magdalena E. Jurzak ,  Dominika Dymitruk ,  Ludmiła Węglarz 

Departament of Biochemistry, Medical University of Silesia, Narcyzow 1, Sosnowiec 41-200, Poland


Tumor metastasis is one of the main cause of the poor prognosis in patients with colon cancer. Degradation of collagen type IV, a major component of the basement membrane, is an essential step in the metastasis to lymph nodes and distant organs. Matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) belong to zinc and calcium dependent family of enzymes that digeste collagen IV and other components of extracellular matrix. Moreover, MMPs participate in the regulation of cytokines, growth factors and adhesive molecules activity as well as in angiogenesis and apoptosis. The main cellular inhibitors of the matrix metalloproteinases are their tissue inhibitors (TIMPs), supplying a closely regulated mechanism for control, activation and function of MMPs. Inositol hexaphosphate (phytic acid, IP6), a ubiquitous plant component, plays a role in the control of tumor growth, progression, and metastasis. One postulated mechanism by which IP6 prevents the activation of MMPs may be due to its ability to chelate minerals such as iron, copper, zinc, cobalt, and manganese. The aim of the presented study was to evaluate the expression profile of MMP-2, MMP-9 and their tissue inhibitors at the mRNA level in human colorectal cancer cell line Caco-2 treated with phytic acid. A kinetic study of MMP-2, MMP-9 and TIMP-1, TIMP-2 mRNAs was performed on Caco-2 cells after 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 1mM evoked increase in MMP-2 transcript level, however, its higher doses (2,5; 5 mM) caused a decrease in this gene expression at 1h incubation. In 24 h lasting culture along with increasing IP6 concentrations the cells expressed higher and higher MMP-2 mRNA level. In response to 1 mM at 6h, 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 12h 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.


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Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Małgorzata Kapral
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-11 12:06
Revised:   2010-03-11 12:06