The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells

Abstract

IntroductionMatrix 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-1β-stimulated colon cancer cell line Caco-2.Materials and methodsReal-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-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h.ResultsStimulation of cells with IL-1β 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-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6.ConclusionProinflammatory cytokine IL-1β 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-1β 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.

Cytotoxic effect of inositol hexaphosphate and its Ni(II) complex on human acute leukemia Jurkat T cells

“…InsP 6 possesses antiproliferative activities and has therefore been proposed as an antitumor agent (Vucenik et al, 2005;Tian and Song, 2006;Agarwal et al, 2009;Kapral et al, 2012;Deliliers et al, 2002;Singh et al, 2003). In the same way, Ni(II) has been described as an important cytotoxic agent and apoptosis inductor (Ada et al, 2010;Chen et al, 2010).…”

“…The InsP 6 influences constitutive expression of metalloproteinase, MMP and TIMP (tissue inhibitors of MMPs) genes and downregulates IL-1β stimulated transcription of some of these genes. InsP 6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion (Kapral et al, 2012). Physiological intestinal concentrations of InsP 6 may have an Toxicology in Vitro 29 (2015) …”

Distinct Transcriptional Changes and Epithelial–Stromal Interactions Are Altered in Early-Stage Colon Cancer Development

“…We also observed TIMP-2 upregulation in BRAF and KRAS-mutant ACF, although the effect of TIMP-2 on tumor progression is less well-defined (40). Some studies have correlated high levels of TIMP-2 with an adverse prognosis (41,42), while other studies have observed an opposite effect (43–45). The general consensus, however, is that overexpression of TIMP family proteins elicit effects on ECM turnover and facilitates formation of the tumor microenvironment.…”

Downregulation of telomerase maintenance-related ACD expression in patients undergoing immunosuppresive therapy following kidney transplantation

“…A standard curve method was used to quantify the RT-qPCR results for hTERT, ACD, DKC1 and GAPDH (24,25). Commercially available β-actin cDNA standards (TaqMan ® DNA Template Reagent kit; Applied Biosystems) were used at 0.6, 1.2, 3.0, 6.0 and 12.0 ng/µl to simultaneously detect the expression profile of each of the target genes.…”