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 aim of this study was to analyze the molecular mechanism of inositol hexaphosphate (InsP(6)) action through which it may inhibit proliferation of colon cancer cells and cell cycle progression. A kinetic study of p53 and p21(WAF1) mRNA increase was performed on human colon cancer HT-29 cells after treatment with 1, 5 and 10 mM InsP(6) for 6, 12, 24 and 48 h. Real-time-QPCR based on TaqMan methodology was applied to analyze quantitatively the transcript levels of these genes. The transcription of beta-actin and GAPDH genes was assessed in parallel to select the control gene with least variability. The 2(-Delta Delta Ct) method was used to analyze the relative changes in gene transcription. InsP(6) stimulated p53 and p21(WAF1) expression at the mRNA level, with the highest increase in p21(WAF1) mRNA occurring at 24 h, i.e., following the highest increase in p53 mRNA observed at 12 h. Based on these studies it may be concluded that the ability of InsP(6) to arrest the cell cycle may be mediated by the transcriptional up-regulation of the p53-responsive p21(WAF1) gene.
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PMID:Quantitative analysis of the level of p53 and p21(WAF1) mRNA in human colon cancer HT-29 cells treated with inositol hexaphosphate. 1673 61

Epidemiology has revealed that physical activity is an important lifestyle factor that reduces the risk of colon cancer. However, the underlying mechanisms of this protective effect have so far not been defined. The aim of this study was to identify molecular targets of physical activity in rat colon mucosa by employing our voluntary exercise model. Twenty male rats underwent a 12-week exercise program, with 9 additional rats serving as a control group. Running distances, body weights and heart weights as measures of physical adaptations were recorded, and changes in mRNA steady-state levels of marker genes involved in vascularization (VEGF, HIF-1 alpha, ODC-1), apoptosis (Bcl-2, PPAR gamma) and prostaglandin synthesis (COX-2) were determined by qRT-PCR. The four housekeeping genes GAPDH, beta-actin, 18S and ALDA served as reference genes. Recorded running distances showed great inter-individual differences resulting in three different groups of low (L-EX, < 2629 m/night; n=5), moderate (M-EX, 3003 - 7458 m/night; n=10) and high (H-EX, > 8314 m/night; n=5) physical activity. The M-EX and H-EX group revealed significant (p<0.05) adaptive changes with an increase in heart mass per kg body weight and a decrease in mean body weight. Amongst the marker genes studied by mRNA expression analysis only ODC-1 appears to be differentially expressed. Its 1.8-fold increased steady-state mRNA level in the H-EX group suggests that synthesis of polyamines may be increased by physical activity. This new finding could provide a link between extensive physical activity and its protective effects on colon cancer development.
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PMID:Exercise associated genes in rat colon mucosa: upregulation of ornithin decarboxylase-1. 1711 18

The tumor microenvironment (TME) is critical for tumor growth and progression. We have previously developed color-coded imaging of the TME using a green fluorescent protein (GFP) transgenic nude mouse as a host. However, most donor sources of cell types appropriate for study in the TME are from mice expressing GFP. Therefore, a nude mouse expressing red fluorescent protein (RFP) would be an appropriate host for transplantation of GFP-expressing stromal cells as well as double-labeled cancer cells expressing GFP in the nucleus and RFP in the cytoplasm, thereby creating a three-color imaging model of the TME. The RFP nude mouse was obtained by crossing non-transgenic nude mice with the transgenic C57/B6 mouse in which the beta-actin promoter drives RFP (DsRed2) expression in essentially all tissues. In crosses between nu/nu RFP male mice and nu/+ RFP female mice, the embryos fluoresced red. Approximately 50% of the offspring of these mice were RFP nude mice. In the RFP nude mouse, the organs all brightly expressed RFP, including the heart, lungs, spleen, pancreas, esophagus, stomach, duodenum, the male and female reproductive systems; brain and spinal cord; and the circulatory system, including the heart, and major arteries and veins. The skinned skeleton highly expressed RFP. The bone marrow and spleen cells were also RFP positive. GFP-expressing human cancer cell lines, including HCT-116-GFP colon cancer and MDA-MB-435-GFP breast cancer were orthotopically transplanted to the transgenic RFP nude mice. These human tumors grew extensively in the transgenic RFP nude mouse. Dual-color fluorescence imaging enabled visualization of human tumor-host interaction. The RFP nude mouse model should greatly expand our knowledge of the TME.
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PMID:A transgenic red fluorescent protein-expressing nude mouse for color-coded imaging of the tumor microenvironment. 1909 36

Proanthocyanidins (PCs) have been shown to suppress the growth of diverse human cancer cells and are considered as promising additions to the arsenal of chemopreventive phytochemicals. An oligomeric mixture of PCs from hops (Humulus lupulus) significantly decreased cell viability of human colon cancer HT-29 cells in a dose-dependent manner. Hop PCs, at 50 or 100 microg/ml, exhibited apoptosis-inducing properties as shown by the increase in caspase-3 activity. Increased levels of intracellular reactive oxygen species (ROS) was accompanied by an augmented accumulation of protein carbonyls. Mass spectrometry-based proteomic analysis in combination with 2-alkenal-specific immunochemical detection identified beta-actin and protein disulfide isomerase as major putative targets of acrolein adduction. Incubation of HT-29 cells with hop PCs resulted in morphological changes that indicated disruption of the actin cytoskeleton. PC-mediated hydrogen peroxide (H2O2) formation in the cell culture media was also quantified; but, the measured H2O2 levels would not explain the observed changes in the oxidative modifications of actin. These findings suggest new modes of action for proanthocyandins as anticarcinogenic agents in human colon cancer cells, namely, promotion of protein oxidative modifications and cytoskeleton derangement.
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PMID:Hop proanthocyanidins induce apoptosis, protein carbonylation, and cytoskeleton disorganization in human colorectal adenocarcinoma cells via reactive oxygen species. 1927 Dec 84

Cross-resistance to drugs remains an unsolved problem in cancer chemotherapy. This study elucidates a molecular mechanism of cross-resistance to diverse inhibitors of nicotinamide phosphoribosyltransferase (NAMPT) with anticancer activity. We generated a variant of the human colon cancer cell line HCT116, HCT116RFK866, which exhibited primary resistance to the potent NAMPT inhibitor FK866, and was approximately 1,000-fold less sensitive to the drug than the parental HCT116. HCT116RFK866 was found to be cross-resistant to diverse NAMPT inhibitors, including CHS-828, GNE-617, and STF-118804. Whole-exon sequencing revealed two point mutations (H191R and K342R) in NAMPT in HCT116RFK866, only one of which (K342R) was present in the parental HCT116. Importantly, the protein level, NAMPT enzyme activity, and intracellular NAD+ level were similar between HCT116RFK866 and HCT116. Hence, we investigated NAMPT-binding partners in both cell lines by focused proteomic analyses. The amount of NAMPT precipitated with anti-NAMPT monoclonal antibody was much higher in HCT116RFK866 than in the parental. Furthermore, in HCT116, but not in HCT116RFK866, NAMPT was revealed to interact with POTE ankyrin domain family member E and beta-actin. Thus, these results suggest that NAMPT usually interacts with the two partner proteins, and the H191R mutation may prevent the interactions, resulting in resistance to diverse NAMPT inhibitors.
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PMID:Cross resistance to diverse anticancer nicotinamide phosphoribosyltransferase inhibitors induced by FK866 treatment. 2966 58


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