PMID- 22415590 OWN - NLM STAT- MEDLINE DCOM- 20130318 LR - 20211021 IS - 1432-1262 (Electronic) IS - 0179-1958 (Print) IS - 0179-1958 (Linking) VI - 27 IP - 11 DP - 2012 Nov TI - The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1beta-stimulated colon cancer cells. PG - 1419-28 LID - 10.1007/s00384-012-1445-3 [doi] AB - INTRODUCTION: Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1beta-stimulated colon cancer cell line Caco-2. MATERIALS AND METHODS: Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1beta, 2.5 mM of IP6, and both for 6, 12, and 24 h. RESULTS: Stimulation of cells with IL-1beta only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1beta in 6 h lasting culture. After 12 h, IL-1beta-induced MMP-2 mRNA expression was significantly reduced by IP6. CONCLUSION: Proinflammatory cytokine IL-1beta upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1beta stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion. FAU - Kapral, Malgorzata AU - Kapral M AD - Department of Biochemistry, Medical University of Silesia, 41-200 Sosnowiec, Narcyzow 1, Poland. mkapral@sum.edu.pl FAU - Wawszczyk, Joanna AU - Wawszczyk J FAU - Jurzak, Magdalena AU - Jurzak M FAU - Hollek, Andrzej AU - Hollek A FAU - Weglarz, Ludmila AU - Weglarz L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120315 PL - Germany TA - Int J Colorectal Dis JT - International journal of colorectal disease JID - 8607899 RN - 0 (Interleukin-1beta) RN - 0 (RNA, Messenger) RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - 7IGF0S7R8I (Phytic Acid) RN - EC 3.4.- (Metalloproteases) RN - EC 3.4.24.- (Collagenases) RN - EC 3.4.24.- (Gelatinases) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Caco-2 Cells MH - Collagenases/genetics/metabolism MH - Colonic Neoplasms/*enzymology/*genetics/pathology MH - Gelatinases/genetics/metabolism MH - Gene Expression Regulation, Enzymologic/drug effects MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Humans MH - Interleukin-1beta/*pharmacology MH - Matrix Metalloproteinase 3/genetics/metabolism MH - Metalloproteases/*genetics/metabolism MH - Models, Biological MH - Neoplasm Metastasis MH - Phytic Acid/*pharmacology MH - RNA, Messenger/genetics/metabolism MH - Real-Time Polymerase Chain Reaction MH - Tissue Inhibitor of Metalloproteinases/*genetics/metabolism PMC - PMC3474917 EDAT- 2012/03/15 06:00 MHDA- 2013/03/19 06:00 PMCR- 2012/03/15 CRDT- 2012/03/15 06:00 PHST- 2012/02/29 00:00 [accepted] PHST- 2012/03/15 06:00 [entrez] PHST- 2012/03/15 06:00 [pubmed] PHST- 2013/03/19 06:00 [medline] PHST- 2012/03/15 00:00 [pmc-release] AID - 1445 [pii] AID - 10.1007/s00384-012-1445-3 [doi] PST - ppublish SO - Int J Colorectal Dis. 2012 Nov;27(11):1419-28. doi: 10.1007/s00384-012-1445-3. Epub 2012 Mar 15.