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

The effects of cimetidine and indomethacin on the growth of dimethylhydrazine induced or transplanted intestinal tumours in the rat have been studied. Cimetidine is a histamine type 2 receptor antagonist and indomethacin is an inhibitor of prostaglandin synthesis. Two models of rat intestinal tumours were used: a colon carcinoma line transplantable in syngeneic animals and intestinal tumours induced by dimethylhydrazine treatment of Sprague-Dawley rats. Cimetidine and indomethacin were given in drinking water, alone or in combination. Cimetidine had no effect on the growth of transplanted colon cancer but significantly increased the incidence of chemically-induced tumours, with a tendency toward more invasive and metastatic tumours than in the control animals. Indomethacin did not significantly modify the incidence or other characteristics of the tumours in any of the models. This result is at variance with a protective effect of indomethacin on chemically-induced rat colon cancer previously reported by others.
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PMID:Effects of cimetidine and indomethacin on the growth of dimethylhydrazine-induced or transplanted intestinal cancers in the rat. 649 63

A cell culture line has been established from a colonic tumor induced in a rat by dimethylhydrazine. Indomethacin had no effect on the growth of tumors induced in syngeneic rats by s.c. injection of this cell line. Neither indomethacin, nor prostaglandin E2 modify the growth of this established cell line in vitro or alter its destruction by endotoxin-activated macrophages. Indomethacin has been reported to suppress the growth of colonic tumors induced in rats by various carcinogenic drugs. The difference between these results obtained by others on chemically-induced colon cancer and the data we have obtained with a cell line derived from a similar cancer suggests that cancer cells in established culture may loose their sensitivity to prostaglandins, prostaglandin inhibitors or prostaglandin-dependent effector host cells.
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PMID:Effect of indomethacin on the growth of colon cancer cells in syngeneic rats. 659 58

Indomethacin treatment to rats bearing dimethylhydrazine-induced colonic cancer resulted in increased mortality (p less than 0.01) and a greater incidence of metastases compared to untreated animals with the same stage of disease. It is postulated that indomethacin might have a promotional effect on the spread of autochthonous experimental colon cancer.
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PMID:Enhancement of colonic cancer by indomethacin treatment in dimethylhydrazine pretreated rats. 669 45

Chemoprevention of colorectal cancer has been extensively investigated in animal models and in high-risk human populations with inherited or acquired genetic changes, using anticarcinogenic agents from natural and synthetic sources. To understand active agents using a short-term assay, reliable intermediate biomarkers other than cancer are required as end-points. Endoscopically detectable aberrant crypt foci and adenomas are useful biomarkers in human intervention trials. Indomethacin and other nonsteroidal antiinflammatory drugs (NSAIDs) inhibit carcinogen-induced colon cancer development in rats. It was reported that a number of colorectal polyps in familial adenomatous polyposis patients regress after several months of sulindac treatment. Epidemiological studies have shown that regular use of aspirin and other NSAIDs reduces the risk of colorectal cancers and adenomas. In addition, ursodeoxycholic acid and alpha-difluoromethylornithine, a selective inhibitor of ornithine decarboxylase, have been employed in human intervention trials. Vegetable antioxidants such as carotenoids and flavonoids, omega-3 fatty acids, lactic acid bacteria, and indigestible oligosaccharides may also be promising chemopreventive agents.
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PMID:[An overview on chemoprevention of colorectal cancer]. 969 73

Epidemiological studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of colon cancer. In addition, NSAIDs reduce the number and size of polyps in patients with familial adenomatous polyposis. The mechanisms of the anti-neoplastic effect of NSAIDs are still far from complete understanding, but one possible mechanism is the induction of apoptosis. Several lines of evidence suggest that NSAIDs-induced apoptosis in colon cancer cells are mediated through the cyclooxygenase (COX)-independent pathway. In this study we explored the mechanism of NSAIDs-induced apoptosis in the colon cancer cell line, HT-29. We confirmed that NSAIDs induce apoptosis in HT-29 cells irrespective of their COX-selectivity. Indomethacin enhanced the expression of p21waf-1 in HT-29 cells. However the expression of apoptosis-related genes such as Fas, bcl-2 and bax was not affected by indomethacin. Intra- and extra-cellular calcium chelators, protein tyrosine kinase (PTK) inhibitor, protein kinase A (PKA) inhibitor and protein kinase C (PKC) inhibitors did not influence indomethacin-induced apoptosis in HT-29 cells. We concluded that NSAIDs-induced apoptosis in colon cancer cells may be independent from signals transducted through [Ca++]i, PTK, PKA, PKC or the expression of apoptosis-related genes. In contrast, our results demonstrating the induction of p21waf-1 transcription by NSAIDs suggest the possible association of NSAIDs-induced apoptosis and cell-cycle control in colon cancer cells.
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PMID:Induction of apoptosis in colon cancer cells by nonsteroidal anti-inflammatory drugs. 975 93

Epidemiological and dietary studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colon cancer, possibly through a mechanism involving inhibition of cyclooxygenase (COX)-2, which is overexpressed in premalignant adenomatous polyps and colon cancer. Because ultraviolet light (UV) can induce COX-2 and nonspecific NSAIDs can decrease UV-induced skin cancer, we evaluated the ability of two compounds, celecoxib (a specific COX-2 inhibitor) and indomethacin (a nonspecific NSAID), to block UV-induced skin tumor development in SKH:HR-1-hrBr hairless mice. Mice fed 150 or 500 ppm celecoxib showed a dose-dependent reduction (60% and 89%, respectively) in tumor yield. Indomethacin (4ppm) reduced tumor yield by 78%. Although both acute and chronic UV exposure increased cell proliferation and edema, neither compound reduced these parameters. In contrast, UV-induced prostaglandin synthesis in the epidermis was effectively blocked by both compounds. UV-induced increases in COX-2 expression in skin were also not altered in any of the treatment groups. Similarly, tumors that constitutively express high levels of COX-2 displayed no reduction by treatment with celecoxib or indomethacin. The dramatic protective effects of celecoxib suggests that specific COX-2 inhibitors may offer a way to safely reduce the risk of skin cancer in humans.
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PMID:Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis. 1044 29

Some studies have shown that dietary intake of polyunsaturated fatty acids of the n-3 series may have inhibitory effect on the growth of tumor cells both in vivo and in vitro. However, the cellular and molecular mechanisms by which n-3 fatty acids reduce the growth of tumor cells remain poorly understood. In the present studies, we compared the potency of a variety of n-3 and n-6 fatty acids in modulating the apoptotic cell death in HT-29 colon cancer cells. Of all fatty acids examined, we found that docosahexaenoic acid (22:6n-3; DHA) is a potent inducer of apoptosis in a time- and dose-dependent manner. Indomethacin, a cyclooxygenase inhibitor, is ineffective in blocking the apoptosis induced by DHA, suggesting that DHA-induced apoptosis in HT-29 cells is not mediated through the cyclooxygenase pathway. In contrast, the DHA-induced apoptosis is partially reversed by a synthetic antioxidant, butylated hydroxytoluene, indicating that lipid peroxidation may be involved in apoptotic signaling pathway induced by DHA. DHA treatment decreased bcl-2 levels in association with apoptosis, whereas bax levels remained unchanged. These results suggest that decreased expression of bcl-2 by DHA might increase the sensitivity of cells to lipid peroxidation and to programmed cell death.
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PMID:Docosahexaenoic acid is a potent inducer of apoptosis in HT-29 colon cancer cells. 1109 Feb 57

2'-hydroxycinnamaldehyde (HCA) has been shown to have inhibitory effects on farnesyl protein transferase in vitro, angiogenesis, and tumor cell growth. However, mechanism for these inhibitions remains unknown. As a derivative of HCA, BCA (2'-benzoyl-oxycinnamaldehyde) was synthesized by replacing hydroxyl group with benzoyl-oxyl group. When p53-mutated cancer cell lines (MDA-MB-231 breast cancer cell and SW620 colon cancer cell) were treated with 10 microM HCA or BCA, it induced growth arrest and apoptosis of tumor cells. Markers of apoptosis such as degradations of chromosomal DNA and poly(ADP-ribose) polymerase and activation of caspase-3 were detected after HCA or BCA treatment. BCA-induced apoptosis was blocked by pretreatment of cells with anti-oxidants, glutathione, or N-acetyl-cysteine. In addition, BCA-induced activation of caspase-3 and degradation of poly(ADP-ribose) polymerase were abolished by pretreatment of cells with the anti-oxidants. These results suggest that reactive oxygen species are major regulator of BCA-induced apoptosis. HCA or BCA-induced accumulation of reactive oxygen species was detected by using DCF-DA, an intracellular probe of oxidative stress. Furthermore, when BCA (100 mg/kg) was administrated intraperitoneally or orally into a nude mouse, it inhibited >88 or 41% of tumor growth, respectively, without any detectable weight change. These results suggest that BCA is a good drug candidate for cancer therapy.
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PMID:2'-benzoyloxycinnamaldehyde induces apoptosis in human carcinoma via reactive oxygen species. 1466 Jun 55

Heme oxygenase-1 can play a protective role against cellular stress. In colon cancer cells, these effects would be relevant to oncogenesis and resistance to chemotherapy. The aim of the study was to examine the effects of heme oxygenase-1 induction on cell survival in a human colon cancer cell line, Caco-2. Serum deprivation induced apoptosis, reduced Akt and p38 phosphorylation, and increased p21(Cip/WAF1) levels. Heme oxygenase-1 induction by treatment with cobalt protoporphyrin IX resulted in resistance to apoptosis, activation of Akt, reduction in p21(Cip/WAF1) levels and modification of bcl2/bax ratio towards survival. Indomethacin reduced apoptosis but in contrast to heme oxygenase-1, arrested cells in G0/G1. Apoptosis was also inhibited by the heme oxygenase metabolites bilirubin and biliverdin but the CO donor tricarbonyldichlororuthenium(II) dimer did not exert significant effects. Protection against apoptosis in cells treated with cobalt protoporphyrin IX was reverted by incubation with heme oxygenase-1 small interfering RNA. This study shows an antiapoptotic effect of heme oxygenase-1 in colon cancer cells which could be mediated by the formation of bilirubin and biliverdin. Our results support an antiapoptotic role for HO-1 in these cells and provide a mechanism by which overexpression of HO-1 may promote tumor resistance to stress in conditions of limited nutrient supply. We have extended these observations by demonstrating that these effects are independent of p38 but are mediated via Akt pathway.
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PMID:Heme oxygenase-1 inhibits apoptosis in Caco-2 cells via activation of Akt pathway. 1669 92

NSAIDs downregulate survivin (an apoptosis inhibitor), increase apoptosis and reduce growth of colon polyps and cancers. Recently, anti- and pro-apoptosis isoforms of survivin were identified. The roles of these isoforms in NSAID-induced colon cancer cell death have not been examined, and is the focus of this study. The anti-apoptosis isoforms, wild-type (WT) survivin and survivin-DeltaEx3, and the pro-apoptosis isoform, survivin-2b, were present in HT-29 and RKO cells. Indomethacin treatment significantly decreased WT survivin and survivin-DeltaEx3 (30.5+/-10.4% and 20.3+/-6.7%, respectively) but not survivin-2b mRNA in RKO cells. In HT-29 cells, all three isoform mRNAs were slightly decreased by indomethacin treatment. Consistently, indomethacin treatment dramatically reduced WT survivin protein in RKO but not HT-29 cells. Indomethacin treatment increased apoptosis and general cell death more significantly in RKO cells (75.7+/-1.1% cell death at 48 h) than in HT-29 cells (25.4+/-3.7% cell death at 48 h). Anti-sense suppression of survivin-2b mRNA increased resistance of both RKO and HT-29 cells to indomethacin. These data support a role for survivin isoforms in colon cancer cell apoptosis, and thus in prevention of colon cancer growth by NSAIDs.
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PMID:Roles of survivin isoforms in the chemopreventive actions of NSAIDS on colon cancer cells. 1715 52


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