Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antimetastatic properties of soybean saponin were investigated by evaluating matrix metalloproteinase (MMP-2 and MMP-9) production in HT-1080 cells. The mRNA expression levels of MMP-2 and MMP-9 were determined by RT-PCR analysis. The levels of secreted MMP-2, MMP-9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) were determined by gelatin zymography and/or ELISA. The invasion of a Matrigel-coated membrane by human fibrosarcoma HT-1080 and HT-29 colon cancer cells was quantitatively assessed by counting the migrated cells. The treatment of HT-1080 cells with soybean saponin inhibited the mRNA expression of and reduced the amounts of secreted MMP-2 and MMP-9, whereas it increased the amount of secreted TIMP-2 dose-dependently. Soybean saponin significantly inhibited the invasion of HT-1080 cells through a Matrigel-coated membrane. The antimetastatic properties by soybean saponin were further confirmed by in vivo mice experiment via the tail vein injection of CT-26 colon cancer cells after feeding the mice the dietary soybean saponin. The incidence of metastatic tumor colonization of lungs of mice moderately decreased 2 weeks after the tail vein injection of CT-26 cells. Our current data support the notion that soybean saponin inhibits tumor cell metastasis by suppressing MMP-2 and MMP-9 productions, and stimulating TIMP-2 secretion, thereby suggesting that soybean saponin has a chemopreventive property against cancer metastasis.
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PMID:Soybean saponin inhibits tumor cell metastasis by modulating expressions of MMP-2, MMP-9 and TIMP- 2. 1808 15

Tumor cells can stimulate matrix metalloproteinase (MMP) production by stromal cells through cell-cell interactions mediated by cell adhesion molecules such as extracellular matrix metalloproteinase inducer (human CD147/EMMPRIN, mouse CD147/Basigin). This study sought to characterize whether specific tumor-stromal cell interactions mediated by CD147 promote colon cancer growth by utilizing small interfering (si)RNAs directed against human CD147/EMMPRIN or mouse CD147/Basigin in co-cultures of cancer cells with macrophages and fibroblasts and established human SW620 colon cancer xenograft models in immune deficient mice. We show that blockade of host (mouse) CD147/Basigin expression, but not cancer cell-derived CD147/EMMPRIN, suppresses tumor growth in human colon cancer xenografts. Experiments in vitro indicated that colon cancer cell-stromal cell interactions mediated by CD147 lead to increased MMP-2 expression in fibroblasts but not macrophages. Furthermore, expression of host VEGF-A in both fibroblasts and macrophages is independent of CD147 in vitro and in vivo. Interestingly, inhibition of cancer cell-derived EMMPRIN leads to increased MMP-9 levels in vivo. Our findings provide new insights into CD147-mediated tumor-host interactions mediating colon cancer growth.
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PMID:Host CD147 blockade by small interfering RNAs suppresses growth of human colon cancer xenografts. 1850 6

Integrin alphaupsilonbeta6 plays a very important role in the progression of colon cancer cells and is now defined as a novel, independent prognostic indicator for aggressive colon cancer in humans. Herein, we use the RNA interfering technology to downregulate the expression of alphaupsilonbeta6 in colon cancer cells. Our data demonstrate that plasmid vector based shRNA can effectively down-regulate alphaupsilonbeta6 expression in protein and mRNA levels. Supression of integrin alphaupsilonbeta6 inhibits the phosphorylation and nonphosphorylation level of ERK1/2, the secretion of uPA, pro-MMP-9 and pro-MMP-2 in tumor conditioned medium, and more important, inhibits MAPK-dependent [(3)H] labeled collagen IV degradation via the plasminogen activation cascade. Our study demonstrates in vitro that supression of integrin alphaupsilonbeta6 inhibits extracellular matrix degradation through the MAPK pathway.
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PMID:Suppression of integrin alphaupsilonbeta6 by RNA interference in colon cancer cells inhibits extracellular matrix degradation through the MAPK pathway. 1856 96

Several lines of evidence support an important role of TGF-beta in the development of colorectal cancer, although the molecular consequences are largely unknown. Soluble transforming growth factor-beta receptor type II (sTbetaRII) is a target of transforming growth factors-beta (TGF-beta) that plays an important role in regulation tumorigenesis, angiogenesis and metastasis of cancer. To elucidate whether overexpression of sTbetaRII could antagonize TGF-beta in colon cancer cells, we constructed a plasmid that contains a cDNA encoding human extracellular region of TbetaRII and transfected this construction into LoVo cells. Surprisingly, in the absence of TGF-beta1, the overexpression of sTbetaRII antagonized TGF-beta-induced cell proliferation, invasion, motility and angiogenesis, and decreased expression of VEGF and MMP-9. Also, sTbetaRII inhibited TGF-beta-induced apoptosis and improved the induction of antitumor immunity. Our data indicated that sTbetaRII attenuated the biological activities of TGF-beta, suggesting that sTbetaRII may have a therapeutic benefit in colorectal cancer.
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PMID:Soluble transforming growth factor beta type II receptor attenuates TGF-beta1 activity in human colorectal cancer LoVo cells. 1902 Jul 27

This study investigated the effect of arginine (Arg) supplementation on angiogenesis in human colon cancer. The in vitro study investigated the effects of different Arg levels and inducible nitric oxide (iNO) synthase inhibitor on angiogenic protein expressions stimulated by SW480 cells. The results showed that the production of vascular endothelial growth factor (VEGF), basic fibroblast growth factor with 100 and 1000 micromol/L Arg and matrix metalloproteinase (MMP)-2 with 1000 micromol/L Arg was lower than that with 0 and 50 micromol/L Arg. Inhibition of iNO resulted in higher angiogenic protein expressions comparable with groups with low Arg administration, indicating that Arg administration at levels similar to or higher than physiological concentrations reduced the progression of colon cancer, and iNO may partly play a role in reducing angiogenesis. The in vivo study used a human colon cancer xenograft model in nude mice. Mice were inoculated with 1x10(7) SW480 cells and assigned to two groups. The control group was fed a semipurified diet, while the experimental group was supplied an Arg-supplemented diet. After 5 weeks, tumors were harvested and spleens were excised for further analysis. Results showed that the MMP-2, MMP-9 and VEGF receptor levels in tumors were significantly lower, whereas tumor NO levels and spleen natural killer (NK) cell activities were higher in the Arg group than in the control group. These results were consistent with the in vitro study that dietary Arg supplementation inhibits the progression of colon cancer possibly by increasing NO secretion and consequently enhancing NK cell activity.
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PMID:Effect of arginine on angiogenesis induced by human colon cancer: in vitro and in vivo studies. 1944 18

Colon carcinoma invasiveness is a process involving cell-cell and cell-matrix alterations, local proteolysis of the ECM (extracellular matrix) or changes in cytokine and growth factor levels. In order to evaluate the role of TGF-beta1 (transforming growth factor-beta1) and small G protein RhoA in tumour progression, the influence of TGF-beta1 treatment or RhoA-associated kinase inhibitor on the production of NO (nitric oxide) and MMP-2 and MMP-9 (metalloproteinases-2 and -9) was analysed in three human colon adenocarcinoma cell lines (HT29, LS180, SW948) representing different stages of tumour development. All the tested cell lines produced low amounts of MMP-2 and MMP-9. rhTGF-beta1 and the synthetic Rho kinase inhibitor (Y-27632) decreased MMP-2 secretion by colon cancer cells, especially in the most advanced stage of colon cancer. rhTGF-beta1 decreased NO secretion by cells, while Y-27632 had no effect on it. Immunoblotting with anti-RhoA antibodies followed by densitometry revealed that RhoA levels were slightly increased after incubation of colon carcinoma cells (SW948) with rhTGF-beta1. rhTGF-beta1 induced alpha-smooth muscle actin (alpha-SMA) expression, especially in high Duke's grade of colon cancer, while Y-27632 blocked it. Summing up, in colon carcinoma cells, TGF-beta1 and RhoA protein may regulate tumour invasiveness measured as MMP, NO and alpha-SMA expression or assayed using motility data and may be a good target for cancer therapy.
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PMID:Transforming growth factor-beta1 modulates metalloproteinase-2 and -9, nitric oxide, RhoA and alpha-smooth muscle actin expression in colon adenocarcinoma cells. 1994 19

We isolated anthocyanins from fruits of Vitis coignetiae Pulliat, characterized the anthocyanin profile, and investigated the anti-invasive effects of the anthocyanins on human colon cancer cells. The anthocyanins inhibited cell invasion in a dose-dependent manner, as measured by Matrigel invasion assays, by suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression. The anti-invasive activity of the anthocyanins was associated with modulation of constitutive nuclear factor kappaB (NF-kappaB) activation. The activation of NF-kappaB triggered by tumor necrosis factor-alpha was also inhibited by the anthocyanins through suppression IkappaBalpha phosphorylation. AIMs inhibited the expression of NF-kappaB-regulated proteins. In conclusion, this study suggested that the anthocyanins isolated from fruits of V. coignetiae Pulliat should have anti-invasive activities on human colon cancer cells and the activities should be related to the inhibition of NF-kappaB-regulated proteins such as MMP-2 and MMP-9 expression through the inhibition of NF-kappaB activation.
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PMID:Characterization of a profile of the anthocyanins isolated from Vitis coignetiae Pulliat and their anti-invasive activity on HT-29 human colon cancer cells. 2006 25

Dauricine, a bioactive component of Asiatic Moonseed Rhizome, has been widely used to treat a large number of inflammatory diseases in traditional Chinese medicine. In our study, we demonstrated that dauricine inhibited colon cancer cell proliferation and invasion, and induced apoptosis by suppressing nuclear factor-kappaB (NF-kappaB) activation in a dose- and time-dependent manner. Addition of dauricine inhibited the phosphorylation and degradation of IkappaBalpha, and the phosphorylation and translocation of p65. Moreover, dauricine down-regulated the expression of various NF-kappaB-regulated genes, including genes involved cell proliferation (cyclinD1, COX2, and c-Myc), anti-apoptosis (survivin, Bcl-2, XIAP, and IAP1), invasion (MMP-9 and ICAM-1), and angiogenesis (VEGF). In athymic nu/nu mouse model, we further demonstrated that dauricine significantly suppressed colonic tumor growth. Taken together, our results demonstrated that dauricine inhibited colon cancer cell proliferation, invasion, and induced cell apoptosis by suppressing NF-kappaB activity and the expression profile of its downstream genes. These findings provide evidence for a novel role of dauricine in preventing or treating colon cancer through modulation of NF-kappaB singling pathway.
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PMID:Dauricine induces apoptosis, inhibits proliferation and invasion through inhibiting NF-kappaB signaling pathway in colon cancer cells. 2050 40

Head and neck cancers are known to synthesize arachidonic acid metabolites. Interfering with arachidonic acid metabolism may inhibit growth and invasiveness of cancer cells. In this study we investigate effects of sulindac (the non-selective COX inhibitor), aspirin (the irreversible, preferential COX-1 inhibitor), NS-398 (the selective COX-2 inhibitor), NDGA (nordihydroguaiaretic acid, the selective LOX inhibitor) and ETYA (5,8,11,14-eicosatetraynoic acid, the COX and LOX inhibitor) on cell viability, MMP-2 and MMP-9 activities, and in vitro invasion of cancer cells derived from primary and metastatic head and neck, and colon cancers. The inhibitors of COX and/or LOX could inhibit cell proliferation, MMP activity and invasion in head and neck and colon cancer cells. However, the inhibitory effect was obviously observed in colon cancer cells. Inhibition of arachidonic acid metabolism caused a decrease in cancer cell motility, which partially explained by the inhibition of MMPs. Therefore, COX and LOX pathways play important roles in head and neck cancer cell growth.
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PMID:Inhibition of arachidonic acid metabolism decreases tumor cell invasion and matrix metalloproteinase expression. 2065 27

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.
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PMID:Evaluation of the expression of metalloproteinases 2 and 9 and their tissue inhibitors in colon cancer cells treated with phytic acid. 2122 78


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