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)

In order to identify genes which could predict chemosensitivity in colorectal cancer, gene expression and chemosensitivity were examined in colorectal cancer cell lines. Gene expression profiling of 5 colorectal cancer and 3 normal cell lines was performed using a 22K spotted oligonucleotide microarray. The IC50s of 17 anticancer drugs were determined using the MTT assay for chemosensitivity. The SOURCE database, KEGG Pathway database, and Molecular Diagnosis Score (MDS) were used for data analysis. Two representative colorectal cancer cell lines were identified which were resistant or sensitive to drugs commonly used for colon cancer treatment (5-FU, irinotecan and topotecan). Six hundred and eighty-three genes that were up- or down-regulated by >4-fold between the two cell lines were selected. Pathway analysis was performed with 147 of the 683 genes using the KEGG Pathway database. This analysis revealed 27 genes in the apoptosis, MAPK signaling, and focal adhesion pathways, which could explain the mechanism of chemosensitivity in colorectal cancer cell lines. In addition, the chemosensitivity of other colorectal cancer and normal cell lines was predictable with the selected 27 genes. These genes may act as putative predictive markers for chemosensitivity in chemo-naive colorectal cancer patients following functional analysis and clinical validation.
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PMID:Putative chemosensitivity predictive genes in colorectal cancer cell lines for anticancer agents. 1767 6

By using a non-cancer and a cancer cell line originally from the same tissue (colon), coupled with testing lectins for cell binding and for their effects on these cell lines in culture, this study describes a simple multi-parameter approach that has revealed some interesting results that could be useful in drug development strategies. Two human cell lines, CCL-220/Colo320DM (human colon cancer cells, tumorigenic in nude mice) and CRL-1459/CCD-18Co (non-malignant human colon cells) were tested for their ability to bind to agarose microbeads derivatized with two lectins, peanut agglutinin (Arachis hypogaea agglutinin, PNA) and Dolichos biflorus agglutinin (DBA), and the effects of these lectins were assessed in culture using the MTT assay. Both cell lines bound to DBA-derivatized microbeads, and binding was inhibited by N-acetyl-D-galactosamine, but not by L-fucose. Neither cell line bound to PNA-derivatized microbeads. Despite the lack of lectin binding using the rapid microbead method, PNA was mitogenic in culture at some time points and its mitogenic effect displayed a reverse-dose response. This was also seen with effects of DBA on cells in culture. While this is a simple study, the results were statistically highly significant and suggest that: (1) agents may not need to bind strongly to cells to exert biological effects, (2) cell line pairs derived from diseased and non-diseased tissue can provide useful comparative data on potential drug effects and (3) very low concentrations of potential drugs might be initially tested experimentally because reverse-dose responses should be considered.
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PMID:Lectin binding and effects in culture on human cancer and non-cancer cell lines: examination of issues of interest in drug design strategies. 1770 52

The resistance of transformed colon epithelial cells to immune system-mediated extrinsic apoptosis allows the development of fast growing colon cancer. Several tactics have been shown to clarify how colon adenocarcinomas avoid cell deletion and remain viable. Regardless of the presence of active membrane receptors, colorectal cancer cells resist interferon-mediated cell death. Similarly, they are refractory to TNF-alpha-dependent apoptosis. In our studies, we assumed that IFN-R and TNF-R1 receptors compete for STAT-1alpha kinase. Western blot and immunoprecipitation analyses were used to evaluate the protein to protein interactions. Cell viability was measured by MTT assay. We observed that STAT-1alpha kinase is bound to TRADD protein in TNF-R1 signalosome irrespective of the TNF-R1 bound ligand. The amount of STAT-1alpha kinase associated with TRADD was diminished after pretreatment with IFNs. IFN-alpha stimulated the survival of COLO 205 cells rather than promoted cell death. The latter was accompanied by NF-kappaB activation, a fact known to promote anti-apoptosis. STAT-1alpha renders colon adenocarcinoma COLO 205 cells less susceptible to TNF-alpha-induced apoptosis but IFN-alpha further extends the immune escape.
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PMID:IFN-alpha competes with TNF-alpha for STAT-1alpha; molecular basis for immune escape of human colon adenocarcinoma COLO 205 cells. 1778 71

One proposal to increase the efficiency of photodynamic therapy (PDT) is to accompany photosensitization with other treatment modalities, including modulation of arachidonic acid (AA) metabolism. The aim of this study was to evaluate the effectiveness of a combined modality approach employing 48 and 24 h pretreatment with various inhibitors of lipoxygenase (LOX; nordihydroguaiaretic acid, esculetin, AA-861, MK-886 and baicalein), cyclooxygenase (COX; diclofenac, flurbiprofen, ibuprofen, indomethacin, SC-560 and rofecoxib) and cytochrome P450-monooxygenase (proadifen) pathways, followed by hypericin-mediated PDT. Cytokinetic parameters like MTT assay, adherent and floating cell numbers, viability and cell cycle distribution analysis were examined 24 h after hypericin activation. Pretreatment of human colon cancer cells HT-29 prior to PDT with 5-LOX inhibitor MK-886 as well as 5, 12-LOX and 12-LOX inhibitors (esculetin and baicalein, respectively) resulted in significant and dose-dependent effects on all parameters tested. Pretreatment with diclofenac, flurbiprofen, ibuprofen and indomethacin, the nonspecific COX inhibitors, promoted hypericin-mediated PDT, but these effects were probably COX-independent. In contrast, application of SC-560 and rofecoxib, specific inhibitors of COX-1 and COX-2, respectively, attenuated PDT. Inhibition of P450 monooxygenase with proadifen implied also the significance of this metabolic pathway in cell survival and cell resistance to hypericin photocytotoxicity. In conclusion, our results testify that application of diverse inhibitors of AA metabolism may have different consequences on cellular response to hypericin-mediated PDT and that some of them could be considered for potentiation of PDT.
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PMID:Modulation of hypericin photodynamic therapy by pretreatment with 12 various inhibitors of arachidonic acid metabolism in colon adenocarcinoma HT-29 cells. 1788 May 12

Colorectal cancer is the third most common cause of cancer-related deaths in the world. Surgical intervention followed by chemotherapy remains the primary approach to treatment since colon cancers remain refractory to most chemotherapeutic agents. Based on that, we established a program to screen natural products for cytotoxic activity, employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay system utilizing HT-29 human colon cancer cells. During the course of our screening, we found that the methanolic extract of silkworm droppings (SDME) has cytotoxic effects on HT-29 cells. In the present study, we investigated the possible mechanisms by which SDME exerts its antiproliferative activity in HT-29 cells. As expected, SDME inhibited growth of HT-29 cells in a dose-dependent manner as assessed by the MTT reduction assay, the lactate dehydrogenase release assay, and the colony formation assay. We also investigated whether the apoptotic effects induced by SDME involve the caspase pathway using the caspase colorimetric assay. Interestingly, caspase-9 and -3, but not caspase-8, were activated in response to SDME treatment. Taken together, these results clearly indicate that the induction of apoptosis by SDME involves a mitochondrial-mediated pathway and strongly suggest that SDME may potentially be a chemotherapeutic agent for human colon cancer.
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PMID:Effect of methanolic extract from silkworm droppings on proliferation and caspase activity in HT-29 human colon cancer cells. 1788 40

Hesperidin, a known flavonoid constituent of citrus, reduces the proliferation of many cancer cells. The apoptotic effects of hesperidin on human colon cancer cells, SNU-C4, were determined at concentrations of 1-100 microM. At 100 microM, hesperidin reduced cell viability to 65.00+/-0.05% of control values in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell death induced by hesperidin showed apoptotic features in 4,6-diamidino-2-phenylindole (DAPI) staining and in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays. Examination of the expression of apoptosis-regulating genes indicated that hesperidin treatment decreased the expression of B-cell CLL/lymphoma 2 (BCL2) mRNA, and increased the expression of BCL2-associated X protein (BAX). The expression and activity of the major apoptotic factor caspase3 (CASP3) was increased significantly with hesperidin treatment. Hesperidin down-regulated the protein expression of pro-CASP3, and up-regulated the level of active CASP3. Thus, these results suggest that hesperidin could induce apoptosis in human colon cancer cells through CASP3 activation.
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PMID:Apoptotic effect of hesperidin through caspase3 activation in human colon cancer cells, SNU-C4. 1789 17

This study was conducted to evaluate the growth and NAG-1 gene expression effected by Non-steroidal anti-inflammatory drug (NSAID) on colon cancer cell lines in vitro. The proliferation of colon cancer cells were determined by MTT assay and COX-2 protein expression were detected by Western blot. Total RNA was isolated from three kinds of colon cancer cell lines; the expressions of NAG-1 mRNA in the cells treated with or without NSAIDs were assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay. Celecoxib, meloxicam and aspirin were able to inhibit the growth of HT-29, SW480 and LS174-T cells in dose-dependent manner. COX-2 protein expressed in HT-29 and LS174-T, but not in SW480 cells. All of colon cancer cells expressed NAG-1 gene and the level of LS174-T was lower than that of the other two cell lines. NAG-1 expression was increased by treatment with some NSAIDs in all three kinds of colon cancer cells. NSAIDs were able to potentially inhibit the growth of colon cell lines. Induction of NAG-1 gene expression by NSAID was not consistent with COX-2 expression.
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PMID:[Induction of NAG-1 gene expression in colon cancer cells by non-steroidal anti-inflammatory drugs]. 1789 65

Nanodiamond materials can serve as highly versatile platforms for the controlled functionalization and delivery of a wide spectrum of therapeutic elements. In this work, doxorubicin hydrochloride (DOX), an apoptosis-inducing drug widely used in chemotherapy, was successfully applied toward the functionalization of nanodiamond materials (NDs, 2-8 nm) and introduced toward murine macrophages as well as human colorectal carcinoma cells with preserved efficacy. The adsorption of DOX onto the NDs and its reversible release were achieved by regulating Cl- ion concentration, and the NDs were found to be able to efficiently ferry the drug inside living cells. Comprehensive bioassays were performed to assess and confirm the innate biocompatibility of the NDs, via real-time quantitative polymerase chain reaction (RT-PCR), and electrophoretic DNA fragmentation as well as MTT analysis confirmed the functional apoptosis-inducing mechanisms driven by the DOX-functionalized NDs. We extended the applicability of the DOX-ND composites toward a translational context, where MTT assays were performed on the HT-29 colon cancer cell line to assess DOX-ND induced cell death and ND-mediated chemotherapeutic sequestering for potential slow/sustained released capabilities. These and other medically relevant capabilities enabled by the NDs forge its strong potential as a therapeutically significant nanomaterial.
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PMID:Active nanodiamond hydrogels for chemotherapeutic delivery. 1791 3

CD44, a widely distributed cell surface glycoprotein and a receptor for hyaluronan (HA), has been implicated in facilitating tumor growth and metastasis, antiapoptosis and directional motility of cancer cells. In order to investigate the role of soluble CD44 (CD44(sol)) in colon cancer cell growth, SW620, a human colon cancer cell line deficient in CD44 expression was stably transfected with human CD44 cDNA containing exons 1-5, 15 and 16 of the human CD44. Western blot analyses demonstrated the presence of 78 kDa soluble CD44 protein in the culture supernatant of stably transfected cell lines (CD44(sol) clones) and were not detected in the empty vector control line (clone m). The CD44(sol) transfected cells showed higher cell proliferation and clonal growth in vitro, confirmed by MTT and clonogenic assays respectively, when compared to the control cells. Cell adhesion to hyaluronan was significantly lower with CD44(sol) cells compared to the control cells. Western blot analyses were negative for cleaved PARP in lysates from CD44(sol) cells, suggesting resistance to apoptosis. These findings indicate that the secretion of soluble CD44 contributes to colon cancer growth in vitro, possibly as a decoy receptor.
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PMID:Soluble CD44 secretion contributes to the acquisition of aggressive tumor phenotype in human colon cancer cells. 1794 13

The effect of Haeamtang (HAT) on the colon cancer HT-29 cells was investigated in this study. A water extract of HAT significantly decreased the number of HT-29 cells in a dose-and time-dependent manner as determined by a MTT assay. Flow cytometry results revealed a dose- and time-dependent increase of dead cells in HT-29 cells treated with HAT extract. The anticancer activity of the H AT extract is attributed to apoptosis induced in HT-29 cells, which was demonstrated by increased caspase-3 activity and poly-ADP-ribose polymerase fragmentation. A selective caspase inhibitor, z-VAD-fmk, inhibited the HAT-induced cell death. Taken together, these results demonstrate that HAT extract induces apoptosis in HT-29 cells.
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PMID:Haeamtang induces apoptosis of colon cancer HT-29 cells through activation of caspase-3. 1796 28


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