title: Evaluation of the expression of metalloproteinases 2 and 9 and their tissue inhibitors in colon cancer cells treated with phytic acid.
abstract: 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.
authors.affiliation: Department of Biochemistry, Medical University of Silesia, Narcyzów 1, 41-200 Sosnowiec, Poland. mkapral@sum.edu.pl
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kapral
authors.forename: Joanna
authors.initials: J
authors.lastname: Wawszczyk
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jurzak
authors.forename: Dominika
authors.initials: D
authors.lastname: Dymitruk
authors.forename: Ludmiła
authors.initials: L
authors.lastname: Weglarz
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018938:Caco-2 Cells; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D010833:Phytic Acid / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D010833:Phytic Acid; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9