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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six ruthenium derivatives were evaluated in vitro in two human colon cancer cell lines (SW707 and SW948) utilizing the microculture tetrazolium test (MTT) and cell counting with a Coulter Counter. The ruthenium compound sodium-(tetrachloroimidazoledimethylsulfoxideruthenate)- bisdimethylsulfoxide (Na(RuDMSOimCl4)) showed the best efficacy in inhibiting cell proliferation of both colon cancer cell lines followed by the other DMSO ruthenium compound sodium-(tetrachloroindazoledimethylsulfoxideruthenate) - bisdimethylsulfoxide (Na(RuDMSOIndCl4)), as demonstrated by IC50 values (80 and 90 micrograms/ml in SW707 and SW948 cell lines for Na(RuDMSOImCl4); 155 and 165 micrograms/ml in SW707 and SW948 cell lines for Na(RuDMSOIndCl4), respectively). Out of the ruthenium derivatives without DMSO, transindazolium - [tetrachlorobis(1H - indazole)ruthenate (III,N2)] (HInd[RuInd2Cl4(N2)]), was as active as its DMSO-containing congener whereas trans-imidazolium- [tetrachlorobisimidazoleruthenate)(III)], (HIm(RuIm2Cl4)) was less active, as shown by the IC50 values: (HIm (RuIm2Cl4) = 250 and 260 micrograms/ml in cell lines SW707 and SW948; HInd[RuInd2Cl4(N2)] = 110 and greater than 200 micrograms/ml in cell lines SW707 and SW948, respectively). The other ruthenium derivatives containing pyrazole and triazole as ligands (trans - pyrazolium (tetrachlorobispyrazoleruthenate) (III), PzH(RuPz2Cl4) and triazolium(tetrachlorobistriazoleruthenate) (III), TrH(RuTr2Cl4)) were active only at high concentrations that cannot be regarded as realistic in vivo, as shown by the respective IC50 values: (PzH(RuPz2Cl4) = 1056 and 750 micrograms/ml in cell lines SW707 and SW948; TrH(RuTr2Cl4) = 350 and 300 micrograms/ml in cell lines SW707 and SW948). The promising activity of ruthenium compounds with DMSO, indazole and imidazole as ligands should be evaluated in vivo for elucidating their possible role in the treatment of colorectal cancer.
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PMID:Antitumor activity of some ruthenium derivatives in human colon cancer cell lines in vitro. 141 38

This hypothesis paper reviews diverse evidence suggesting that intracolonic production of oxygen radicals may play a role in carcinogenesis. The hypothesis began to evolve when the author made the chance discovery that 1/10,000 dilutions of feces generated detectable quantities of highly reactive hydroxyl radicals (HO.). The rate of HO. formation, detected using DMSO as a molecular probe, was quite remarkable, corresponding to that which would be produced by over 10,000 rads of gamma irradiation per day, absorbed in the periphery of the fecal mass adjacent to the mucosa. The relatively high concentrations of iron in feces, together with the ability of bile pigments to act as iron chelators that support Fenton chemistry, may very well permit efficient HO. generation from superoxide and hydrogen peroxide produced by bacterial metabolism. Such free radical generation in feces could provide a missing link in our understanding of the etiology of colon cancer: the oxidation of procarcinogens either by fecal HO., or by secondary peroxyl radicals (ROO.) to form active carcinogens or mitogenic tumor promotors. Intracolonic free radical formation may explain the high incidence of cancer in the colon and rectum, compared to other regions of the GI tract, as well as the observed correlations of a higher incidence of colon cancer with red meat in the diet, which increases stool iron, and with excessive fat in the diet, which may increase the fecal content of procarcinogens and bile pigments.
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PMID:Free radicals and the etiology of colon cancer. 218 44

To examine the effect of the polar solvents on 1,2-dimethylhydrazine (DMH)-induced colon cancer, 100 male Sprague-Dawley rats were randomly allocated to a control and three treatment groups. Treated animals received N-methylformamide (NMF), dimethylsulfoxide (DMSO), or methylsulfonylmethane (MSM) added to drinking water 1 week before carcinogen injections commenced and for the duration of the experiment. Primary tumors were detected by serial laparotomy under ether anesthesia performed at 2-month intervals and commencing after carcinogen injections had been completed. The average time to tumor onset was significantly delayed in rats receiving NMF and MSM (P = 0.0141 and 0.0398 respectively, Mantel-Haenszel test). In addition, fewer poorly differentiated tumors were noted in treatment groups. No weight loss or toxicity was observed. These findings demonstrate that the polar solvents significantly reduce the latent period to tumor onset in DMH-induced colon cancer and indicate the need to further investigate such compounds as chemopreventive agents.
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PMID:Use of polar solvents in chemoprevention of 1,2-dimethylhydrazine-induced colon cancer. 340 75

Sodium butyrate (NaBu) but not dimethylsulfoxide (DMSO) induced the synthesis of villin, a protein of the brush border microvilli cytoskeleton, in a rat colon cancer cell line. Neither NaBu nor DMSO altered mdr 1-mRNA expression or multidrug resistance (MDR)--associated cellular transport of doxorubicin. These results show that mdr 1 gene expression and activity are independent of other brush border proteins induced by differentiating agents at the apical pole of the epithelial cell.
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PMID:mdr 1 gene-expression and villin synthesis in a colon cancer cell line differentiated by sodium butyrate. 851 66

We have consistently shown that the organoselenium compound 1,4-phenylenebis(methylene)selenocyanate (p-XSC) is a superior cancer chemopreventive agent and less toxic than selenite or certain naturally-occurring selenoamino acids. To elucidate the effects of p-XSC on human colonic mucosa, biopsies from endoscopically normal sigmoid colon of 30 patients with adenomatous polyps were incubated with p-XSC at concentrations of 1, 2 and 5 micromol/l dissolved in dimethylsulphoxide (DMSO). Biopsies incubated with DMSO or pure culture medium served as a control. Proliferating cells were labelled by bromodeoxyuridine immunohistochemistry and the labelling index (LI) was computed. Upper crypt labelling index (LI of crypt compartments 4+5) and Phih value, which are both discriminators of the expansion of the proliferative zone, were significantly lower after incubation with 1 and 5 micromol/l p-XSC, respectively (LI 4+5: 0.8 and 1.0; Phih value: 2.1 and 2.4), as compared with DMSO (LI 4+5: 3.6 and 4.5; Phih value: 7.0 and 8.3) or culture medium (LI 4+5: 3.3 and 4.5; Phih value: 7.2 and 8.1) (P<0.005 and P<0.05 by Friedman's block test). A trend towards lower levels of LI 4+5 (P=0.059) and Phih value (P=0.075) were seen after 2 micromol/l p-XSC incubation compared with DMSO. Since hyperproliferation of colonic crypt cells with expansion of the proliferative zone is regarded as a biomarker of increased cancer risk, the antiproliferative effects of p-XSC especially on upper crypt LI and Phih value may indicate a possible protective effect of this organoselenium compound in the prevention of human colon cancer development.
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PMID:Antiproliferative effect of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) on colonic epithelium of patients with adenomatous polyps in vitro. 1463 23

Colonic carcinogenesis involves the progressive dysregulation of homeostatic mechanisms that control growth. The epidermal growth factor (EGF) receptor (EGFR) regulates colonocyte growth and differentiation and is overexpressed in many human colon cancers. A requirement for EGFR in colonic premalignancy, however, has not been shown. In the current study, we used a specific EGFR antagonist, gefitinib, to investigate this role of the receptor in azoxymethane colonic premalignancy. The azoxymethane model shares many clinical, histologic, and molecular features of human colon cancer. Mice received azoxymethane i.p. (5 mg/kg/wk) or saline for 6 weeks. Animals were also gavaged with gefitinib (10 mg/kg body weight) or vehicle (DMSO) thrice weekly for 18 weeks, a dose schedule that inhibited normal receptor activation by exogenous EGF. Compared with control colonocytes [bromodeoxyuridine (BrdUrd), 2.2+/-1.2%], azoxymethane significantly increased proliferation (BrdUrd, 12.6+/-2.8%), whereas gefitinib inhibited this hyperproliferation (BrdUrd, 6.2+/-4.0%; <0.005). Azoxymethane significantly induced pro-transforming growth factor-alpha (6.4+/-1.3-fold) and increased phospho-(active) EGFR (5.9+/-1.1-fold), phospho-(active) ErbB2 (2.3+/-0.2-fold), and phospho-(active) extracellular signal-regulated kinase (3.3+/-0.4-fold) in premalignant colonocytes. Gefitinib inhibited activations of these kinases by >75% (P<0.05). Gefitinib also significantly reduced the number of large aberrant crypt foci and decreased the incidence of colonic microadenomas from 75% to 33% (P<0.05). Gefitinib concomitantly decreased cell cycle-regulating cyclin D1 and prostanoid biosynthetic enzyme cyclooxygenase-2 in microadenomas, suggesting that these regulators are key targets of EGFR in colonic carcinogenesis. These results show for the first time that EGFR signaling is required for early stages of colonic carcinogenesis. Our findings suggest, moreover, that inhibitors of EGFR might be useful in chemopreventive strategies in individuals at increased risk for colonic malignancies.
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PMID:Epidermal growth factor receptor signaling is required for microadenoma formation in the mouse azoxymethane model of colonic carcinogenesis. 1723 95

The authors' recent discovery that glycogen synthase kinase-3beta (GSK-3beta) participates in colon cancer cells' survival and proliferation prompted us to investigate whether GSK-3beta inhibition alters proliferation of colon cancer cells in vivo. Groups of four or five athymic mice (Balb/c, nu/nu) with subcutaneous xenografts of SW480 human colon cancer cells were treated with dimethyl sulfoxide (DMSO) or different doses (1, 2 and 5 mg/kg body weight) of either small-molecule GSK-3beta inhibitor (SB-216763 and AR-A014418) by intraperitoneal injection three times per week for 5 weeks. Compared with DMSO (a diluent of the GSK-3beta inhibitors) as a control, either GSK-3beta inhibitor significantly inhibited proliferation of cancer cell xenografts in the rodents in a dose-dependent manner. Histochemical and immunohistochemical analysis of tumor xenografts demonstrated a significant, dose-dependent decrease in fractions of proliferating cells and an increase in the incidence of apoptosis of cancer cells in mice treated with either GSK-3beta inhibitor. No adverse events or effects were observed in the rodents during the course of treatment, except for rare lethal accidents due to intraperitoneal injection. Morphological examination showed no apparent pathologic changes in major organs including the lungs, liver, pancreas, kidneys, spleen and large bowel of rodents treated with DMSO and the GSK-3beta inhibitors. The results indicate that the GSK-3beta inhibitors would be a novel class of therapeutic agent for colon cancer.
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PMID:Inhibition of GSK-3 beta activity attenuates proliferation of human colon cancer cells in rodents. 1764 Mar 4

The complexes mer-[RhCl 3(DMSO-kappa S)(pp)] 1a- 5a may be prepared by reaction of mer,cis-[RhCl 3(DMSO-kappa S) 2(DMSO-kappa O)] with the appropriate polypyridyl ligand (pp = bpy, phen, dpq, dppz, dppn) in CH 3OH/H 2O solution at 75 degrees C. The mer isomers of 1a- 5a are stable in chloroform solution but those of 1a and 2a isomerize rapidly to a mixture of fac and mer isomers in DMSO. The complexes are potent in vitro cytotoxic agents and exhibit IC 50 values that are strongly dependent on the size of the polypyridyl ligand. IC 50 values of, respectively, 4.0 (0.5) and 1.9 (0.5), 0.40 (0.06) and 0.19 (0.05), and 0.079 (0.012) and 0.069 (0.021) microM are observed for 1a- 3a against the human cell lines MCF-7 (breast cancer) and HT-29 (colon cancer). Cellular uptake studies showed a rapid and high accumulation of the polypyridyl compounds. Treatment of HT-29 and MCF-7 cells with 3a leads to significant decreases in cellular oxygen consumption and the rate of extracellular acidification.
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PMID:Synthesis, biological activity, and structure-activity relationships for potent cytotoxic rhodium(III) polypyridyl complexes. 1854 1

Cancer chemopreventive activity of sulforaphane has been predominantly associated with its ability to induce phase II detoxification enzymes. In the present study, novel targets of sulforaphane were identified and characterized using a proteomics approach. Two-dimensional gel electrophoresis and mass spectrometry were used to produce protein profiles of human colon adenocarcinoma Caco-2 cells treated with 5 mumol/L sulforaphane for 48 h and control cells (0.05% DMSO). Gel comparisons showed the down-regulation to undetectable level of the serotonin receptor 5-HT(3) after sulforaphane treatment. In addition, Aldo-keto reductase and d-dopachrome decarboxylase were also differentially expressed in control and treated cell extracts. To elucidate two-dimensional gel findings, the neurotransmitter receptors 5-HT(3A), 5-HT(1A), 5-HT(2C), and the serotonin reuptake transporter were analyzed using Western blotting. Results showed a decrease of neurotransmitter receptors in a dose-dependent manner after sulforaphane treatment. Moreover, after exposure of Caco-2 cells to sulforaphane, nicotinic acetylcholine receptor protein level was increased. These findings suggested a potential effect of sulforaphane on serotonin release. Activation of neurotransmitter receptors followed by initiation of cyclic AMP signaling might be crucial events in colon carcinoma progression. Thus, the effect of sulforaphane may help to elucidate signaling pathways serotonin-mediated in colon cancer and lead to development of potential novel therapeutic agents.
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PMID:Serotonin receptors, novel targets of sulforaphane identified by proteomic analysis in Caco-2 cells. 1859 52

Some tuber-bearing wild potato species are reportedly higher in potential health-promoting traits, such as antioxidant activity (AOA) and total phenolic content (TP), than commercial cultivars; therefore, they could be used as parental material in breeding for high AOA and TP. However, using wild species might result in progenies that are toxic for human consumption because of the presence of high total glycoalkaloids (TGAs) and other unknown compounds. Therefore, wild potato accessions should be screened for cytotoxicity before their introduction into breeding programs. The objective of this study was to investigate antiproliferative activity and cytotoxicity of tuber extracts from 15 Solanum jamesii accessions on human HT-29 colon and LNCaP prostate cancer cell lines in vitro. Also, correlations among AOA, TP, TGA, and antiproliferative activity were determined. The tuber extracts significantly inhibited proliferation of HT-29 and LNCaP cell lines and were not cytotoxic to the cells compared to the control (DMSO). The antiproliferative activity exhibited by tuber extracts was not due to necrosis, because the amount of lactate dehydrogenase (LDH) released from cells incubated with the extracts was not significantly different from that released from cells incubated without extracts (control). Colon cancer cells were more responsive to tuber extract treatment than prostate cancer cells. In both HT-29 and LNCaP cells, there were no observable significant correlations between antioxidant activity (DPPH and ABTS) and inhibition of cell proliferation or between TP and cell proliferation inhibition. Also, glycoalkaloids did not exhibit significant correlations with the inhibition of cancer cell proliferation. Findings of this study show that S. jamesii accessions probably pose no cytotoxic effects when used as parental material in improving the nutritional value of potato cultivars. Correlation results, along with cell proliferation data, suggest that not only the compounds measured in this study but also other bioactive compounds present in the matrix acting additively or synergistically may be more responsible for the antiproliferative effects of potato tuber extracts than higher concentrations of a single or group of compounds.
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PMID:Antiproliferative activity and cytotoxicity of Solanum jamesii tuber extracts on human colon and prostate cancer cells in vitro. 1971 17


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