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

Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Cyclooxygenase (COX)-2 plays an important role in colon carcinogenesis. To investigate the effect of curcumin on COX-2 expression, we treated HT-29 human colon cancer cells with various concentrations of curcumin. Curcumin inhibited the cell growth of HT-29 cells in a concentration- and time-dependent manner. Curcumin markedly inhibited the mRNA and protein expression of COX-2, but not COX-1. These data suggest that a non-toxic concentration of curcumin has a significant effect on the in vitro growth of HT-29 cells, specifically inhibits COX-2 expression, and may have value as a safe chemopreventive agent for colon cancer.
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PMID:Specific inhibition of cyclooxygenase-2 (COX-2) expression by dietary curcumin in HT-29 human colon cancer cells. 1156 84

The regular use of various nonsteroidal anti-inflammatory drugs (NSAIDs) was shown to decrease the incidence of colorectal cancer. This effect is thought to be caused predominantly by inhibition of cyclooxygenase-2 (COX-2) and, subsequently, prostaglandin synthesis. However, recent studies have suggested that COX-independent pathways may contribute considerably to these antiproliferative effects. To evaluate the involvement of COX-dependent and COX-independent mechanisms further, we assessed the effects of celecoxib (selective COX-2 inhibitor) and SC560 (selective COX-1 inhibitor) on cell survival, cell cycle distribution, and apoptosis in three colon cancer cell lines, which differ in their expression of COX-2. Both drugs induced a G0/G1 phase block and reduced cell survival independent of whether or not the cells expressed COX-2. Celecoxib was more potent than SC560. The G0/G1 block caused by celecoxib could be attributed to a decreased expression of cyclin A, cyclin B1, and cyclin-dependent kinase-1 and an increased expression of the cell cycle inhibitory proteins p21Waf1 and p27Kip1. In addition, celecoxib, but not SC560, induced apoptosis, which was also independent of the COX-2 expression of the cells. In vivo, celecoxib as well as SC560 reduced the proliferation of HCT-15 (COX-2 deficient) colon cancer xenografts in nude mice, but both substances had no significant effect on HT-29 tumors, which express COX-2 constitutively. Thus, our in vitro and in vivo data indicate that the antitumor effects of celecoxib probably are mediated through COX-2 independent mechanisms and are not restricted to COX-2 over-expressing tumors.
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PMID:COX-2 independent induction of cell cycle arrest and apoptosis in colon cancer cells by the selective COX-2 inhibitor celecoxib. 1160 77

Colorectal cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer deaths in the United States. Efforts to prevent colon cancer have targeted early detection through screening and chemoprevention. For the last ten years our laboratory has utilized an in vivo screening assay for the testing of potential cancer preventives for colon cancer. We have conducted investigations on over 150 compounds including many with botanical or herbal origins. As part of our program on natural products we have examined a number of herbal and botanical products in the aberrant crypt foci (ACF) assay including Korean red ginseng powder, green tea catechins, curcumin from the Indian culinary spice, tumeric, compounds from garlic and onion, resveratrol from red grapes, among others. In the ginseng experiments groups of 10 F344 rats were fed ginseng powder at a dose of 0.5 g/kg or 2 mg/kg for 5 weeks. During weeks 2 and 3 rats were injected with 10 mg/kg azoxymethane to induce ACF. Controls (n=10) did not receive azoxymethane (AOM). Rats were killed by CO2 overdose and ACF counted in the rat colon. In 8 week post-initiation experiments ginseng powder inhibited the progression of established ACF, indicating a cytostatic effect. This may be due to an anti-inflammatory effect. There is a body of literature that suggests that compounds in wine, tumeric, and tea inhibit cyclooxygenases, thus reducing prostaglandin-mediated effects on the colon. As colon tumors have been shown to highly express COX-2 protein, and given, that many NSAID drugs also suppress COX-1, it is tempting to speculate that herbal products that inhibit one or both forms of the COX enzyme will be effective agents for the prevention of cancer in man.
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PMID:Colon cancer chemoprevention with ginseng and other botanicals. 1174 82

Prostaglandins (PGs), bioactive lipid molecules produced by cyclooxygenase enzymes (COX-1 and COX-2), have diverse biological activities, including growth-promoting actions on gastrointestinal mucosa. They are also implicated in the growth of colonic polyps and cancers. However, the precise mechanisms of these trophic actions of PGs remain unclear. As activation of the epidermal growth factor receptor (EGFR) triggers mitogenic signaling in gastrointestinal mucosa, and its expression is also upregulated in colonic cancers and most neoplasms, we investigated whether PGs transactivate EGFR. Here we provide evidence that prostaglandin E2 (PGE2) rapidly phosphorylates EGFR and triggers the extracellular signal-regulated kinase 2 (ERK2)--mitogenic signaling pathway in normal gastric epithelial (RGM1) and colon cancer (Caco-2, LoVo and HT-29) cell lines. Inactivation of EGFR kinase with selective inhibitors significantly reduces PGE2-induced ERK2 activation, c-fos mRNA expression and cell proliferation. Inhibition of matrix metalloproteinases (MMPs), transforming growth factor-alpha (TGF-alpha) or c-Src blocked PGE2-mediated EGFR transactivation and downstream signaling indicating that PGE2-induced EGFR transactivation involves signaling transduced via TGF-alpha, an EGFR ligand, likely released by c-Src-activated MMP(s). Our findings that PGE2 transactivates EGFR reveal a previously unknown mechanism by which PGE2 mediates trophic actions resulting in gastric and intestinal hypertrophy as well as growth of colonic polyps and cancers.
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PMID:Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. 1187 1

Cyclooxygenase (COX) is the crucial enzyme for synthesis of prostaglandins and occurs in two isoforms COX-1 and COX-2. Whilst COX-1 is constantly expressed in the gastrointestinal tract in large quantities and probably maintains mucosal integrity through constant generation of prostaglandins, COX-2 is induced principally during inflammation. In early gastric cancer and in intestinal metaplasia the expression of COX-2 in patients infected by Helicobacter pylori is increased in intestinal type compared to diffuse type gastric cancer and in intestinal metaplasia. In tumours of mixed type, COX-2 is also increased in the intestinal component compared to the diffuse component. Whilst there has been success of COX-2 inhibition for chemoprevention in colon cancer, a similar role in gastric cancer needs to be carefully assessed in the light of reported adverse effects and whether the precancerous condition, intestinal metaplasia, can truly regress.
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PMID:Cyclooxygenase-2 expression in early gastric cancer, intestinal metaplasia and Helicobacter pylori infection. 1194 46

Platelets are implicated in the pathogenesis of various chronic diseases including cancer. The main objective of the present study was to determine if dietary fish oil and piroxicam, known modulators of colon tumorigenesis, effect transforming growth factor (TGF)-betas and cyclooxygenase (COX) isozymes in the platelets of colon tumor-bearing male F344 rats. TGF-betas and COXs are important in the development of chronic illnesses including colon cancer. Animals harboring preneoplastic colonic lesions were randomly allocated to a low fat diet (5% by weight--low corn oil, LFC) and three high fat diets (23% by weight--high corn oil, HFC; high corn oil containing 150-ppm piroxicam, HFC+P; and high fish oil, HFF) for 16 weeks. TGF-beta1, TGF-beta2, COX-1 and COX-2 protein levels were assessed in the platelets by Western blot analysis. Active TGF-beta1 (12.5 kDa) level was significantly lower in the platelets of the HFC+P group (p < 0.001), whereas precursor TGF-beta1 (39 kDa) level was significantly lower in the platelets of the HFF group (p < 0.001). The anti-rabbit TGF-beta2 polyclonal antibody did not detect the 13-kDa active TGF-beta2 protein in the platelets. However a 29-kDa protein, potentially a precursor of TGF-beta2, was detected in the platelets of all the groups and was significantly lower in the HFC+P and HFF groups than in LFC and HFC (p < 0.001). COX-1 level was significantly lower in the HFF group than the other three groups (p < 0.001). COX-2 protein was detected in the platelets of all diet groups. Piroxicam in the presence of high corn oil (HFC+P) significantly lowered the level of COX-2 (p < 0.001), without having any effect on COX-1 level. These findings conclusively show that LFC and HFC differ from HFF and HFC+P, and piroxicam differs from fish oil, in regulating the levels of TGF-betas and COX in the platelets. This supports the conjecture that the levels of bioactive constituents of the platelets are profoundly modulated by dietary lipids, which in turn could influence the pathogenesis of chronic illnesses.
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PMID:Differential modulation of transforming growth factor-betas and cyclooxygenases in the platelet lysates of male F344 rats by dietary lipids and piroxicam. 1195 55

It is well known that about 70% of cancer cases are due to environmental, dietary, or lifestyle factors. Accordingly, these cases maybe avoided by appropriate modifications. In addition, active chemoprevention has become a major interventional approach following the epidemiological observation of a beneficial effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in colon cancer prevention. This is chiefly due to the inhibition of the cyclooxygenase (COX) enzymes. The COX enzymatic system includes two isoenzymes, COX-1 and COX-2, that convert arachidonic acid to prostaglandins. COX-1 is constitutively expressed and synthesizes cytoprotective prostaglandins in the gastrointestinal tract. COX-2 is inducible by the oncogenes ras and scr and other cytokines; it is overexpressed in human cancer cells in which it stimulates cellular division and angiogenesis and inhibits apoptosis. NSAIDs restore apoptosis and decrease tumor mitogenesis and angiogenesis. Most cancer cells have been found to exhibit overexpression of COX-2. Epidemiological studies showed a lower risk of developing cancer of the colon, breast, esophagus, and stomach following the ingestion of NSAIDs. The use of NSAIDs in low dose was associated with a statistically significant decrease in the risk of adenomatous polyps and of overt colon cancer. The regressive effects of sulindac on foci of aberrant crypts in the colon (considered to be precursors of adenoma), and on adenocarcinoma of the colon, are of particular interest because this NSAID does not have an inhibitory effect on COX. This may support the view that the antineoplastic effect of NSAIDs may also be due to a mechanism other than COX-2 inhibition. In breast cancer, large cohort studies reported a 40 to 50% reduced risk of developing cancer, a smaller size of the primary tumor, and a reduction in the number of involved axillary lymph nodes. Similar findings have been reported in the esophagus and stomach, but not in gastric cardia adenocarcinoma. The recent development of selective COX-2 inhibitors resulted in better clinical tolerance than that associated with NSAIDs in general, with the absence of gastrointestinal side effects known to occur after the inhibition of COX-1. Encouraging results have been obtained with these new agents in familial adenomatous polyposis, colon, breast, and prostate cancer.
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PMID:Epidemiological and clinical aspects of nonsteroidal anti-inflammatory drugs and cancer risks. 1208 6

Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) seems to reduce the progression of several diseases, including colon cancer, lung cancer, breast cancer and Alzheimer disease (AD). Several studies have shown that NSAIDs can modulate cell cycle progression, especially in the G0/G1 phase. The main target of most NSAIDs is the enzyme cyclo-oxygenase (COX), which occurs in 2 isoforms, COX-1 and COX-2. In AD and non-demented control brain, COX-2 is expressed in neuronal cells. In this study the expression of COX-2, cyclin D1, and cyclin E was investigated at the immunohistochemical level in AD and non-demented control temporal cortex. COX-2, cyclin D1, and cyclin E expression was detected in pyramidal neurons in both AD and control patients. The number of COX-2-immunoreactive neurons positively correlated with the number of cyclin E- and cyclin D1-immunoreactive neurons. Moreover, immunostaining of sequential tissue sections and double immunofluorescence labeling revealed co-expression of COX-2 and cyclin D1 and E in neuronal cells. In addition, an inverse correlation was observed between the neuronal expression of COX-2 and cyclin E and the Braak score for amyloid beta deposits. Our findings suggest a relationship between the neuronal expression of COX-2 and cell cycle markers, which may be involved early in AD pathology.
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PMID:Cyclin D1 and cyclin E are co-localized with cyclo-oxygenase 2 (COX-2) in pyramidal neurons in Alzheimer disease temporal cortex. 1215 83

Cyclooxygenases-1 and -2 (COX-1 and COX-2, also known as prostaglandin H2 synthases-1 and -2) catalyze the committed step in prostaglandin synthesis. COX-1 and -2 are of particular interest because they are the major targets of nonsteroidal antiinflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2-selective inhibitors. Inhibition of the COXs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces the incidence of fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of COXs relate mechanistically to cyclooxygenase and peroxidase catalysis and how alternative fatty acid substrates bind within the COX active site. We further examine how NSAIDs interact with COXs and how differences in the structure of COX-2 result in enhanced selectivity toward COX-2 inhibitors.
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PMID:The structure of mammalian cyclooxygenases. 1257 66

The role of nitric oxide (NO) in colon cancer remains controversial. Inducible nitric oxide synthase (iNOS) has been reported to be up regulated and down regulated in colorectal cancer in both animal models and patient tissue samples. Cyclooxygenase-2 (COX-2) is important in colorectal carcinogenesis but its relationship with NO has never been studied in colon cancer. Three colon cancer cell lines (HCA7, HT29 and HCT116) with different COX-2 expression and activities were used to study the effect of the NO donor, S-nitrosoglutathione (GSNO). The effects of GSNO (10-500 micro M) on cell growth, PGE(2) production, COX-1/COX-2 protein expression and cell-cycle distribution were evaluated. GSNO increased PGE(2) production and induced COX-1 and COX-2 protein expression in a dose- and time-dependent manner. Higher concentrations of GSNO also inhibited cell growth and induced apoptosis in all three cell lines, regardless of their COX-2 expression/activities. Inhibition of PGE(2) production did not further improve the inhibitory effect of GSNO.
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PMID:Nitric oxide induces cyclooxygenase expression and inhibits cell growth in colon cancer cell lines. 1272 90


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