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

1,2-dimethylhydrazine (DMH) is a colon carcinogen which undergoes oxidative metabolism in the liver. We have investigated the modulatory effect of fenugreek seeds (a spice) on colon tumor incidence as well as hepatic lipid peroxidation (LPO) and antioxidant status during DMH-induced colon carcinogenesis in male Wistar rats. In DMH treated rats, 100% colon tumor incidence was accompanied by enhanced LPO and a decrease in reduced glutathione (GSH) content as well as a fall in glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities. Inclusion of fenugreek seed powder in the diet of DMH treated rats reduced the colon tumor incidence to 16.6%, decreased the LPO and increased the activities of GPx, GST, SOD and CAT in the liver. We report that fenugreek modulates DMH-induced hepatic oxidative stressduring colon cancer
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PMID:Fenugreek seeds modulate 1,2-dimethylhydrazine-induced hepatic oxidative stress during colon carcinogenesis. 1751 51

To evaluate the antitumor and cytotoxic activity of methanol extract of Phyllanthus polyphyllus (MPP) in mice and human cancer cell lines, the antitumor activity of MPP was evaluated against an Ehrlich ascites carcinoma (EAC) tumor model. The activity was assessed using survival time, hematological studies, lipid peroxidation (LPO), antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione S-transferase (GST), solid tumor mass, and short-term in vitro cytotoxicity. The cytotoxic activity of MPP was evaluated using human breast cancer (MCF7), colon cancer (HT29), and liver cancer (HepG2) cell lines Oral administration of MPP (200 and 300 mg/kg) increased the survival time and significantly reduced the solid tumor volume in a dose-dependent manner. Hematological parameters, protein, and packed cellular volume (PCV), which were altered by tumor inoculation, were restored. MPP significantly decreased the levels of LPO, GPx, GST, and significantly increased the levels of SOD and CAT. In a cytotoxicity study against human cancer cell lines, MPP was found to have IC50 values of 27, 42 and 38 microg/ml on MCF-7, HT-29, and HepG2 cells respectively. MPP possessed significant antitumor and cytotoxic activity on EAC and human cancer cell lines.
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PMID:Antitumor and cytotoxic effects of Phyllanthus polyphyllus on Ehrlich ascites carcinoma and human cancer cell lines. 1782 93

Globally, colorectal cancer is the third commonest cancer in men since 1975.The present study focuses on the preventive strategies aimed at reducing the incidences and mortality of large bowel cancer. Chemoprevention of colon cancer appears to be a very realistic possibility because various intermediate stages have been identified preceding the development of malignant colonic tumors. Several studies have demonstrated that generous consumption of vegetables reduces the risk of colon cancer. This idea has prompted the present investigation to search for some novel plant products, which may have possible anticarcinogenic activity. It has already been proved from various experiments that chemopreventive agents, by virtue of their anti-oxidant, anti-inflammatory, anti-proliferative, apoptosis-inducing activity, act at various levels including molecular, cellular, tissue and organ levels to interfere with carcinogens. Previous studies from our laboratory have already reported the inhibitory effect of cinnamon and cardamom on azoxymethane induced colon carcinogenesis by virtue of their anti-inflammatory, anti-proliferative and pro-apoptotic activity. This particular experiment was carried out to assess the anti-oxidative potential of these spices. Aqueous suspensions of cinnamon and cardamom have been shown to enhance the level of detoxifying enzyme (GST activity) with simultaneous decrease in lipid peroxidation levels in the treatment groups when compared to that of the carcinogen control group.
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PMID:Inhibition of lipid peroxidation and enhancement of GST activity by cardamom and cinnamon during chemically induced colon carcinogenesis in Swiss albino mice. 1826 Jul 32

Consumption of cruciferous vegetables has been associated with reduced colon cancer risk in human populations. However, little experimental evidence exists to support this association. Here, we report the effects of diets containing cruciferous vegetables on colon cancer risk. In Expt. 1, rats were fed a vegetable-free (basal) diet or diets containing different lyophilized cruciferous vegetables in concentrations between 4 and 10%. In Expt. 2, rats were fed the basal diet or diets containing 10-22.6% fresh cruciferous vegetables. Diets were fed for 2 wk (Expt. 1) or 3 wk (Expt. 2) before and 7 wk (Expt. 1) or 12 wk (Expt. 2) after administration of the colon carcinogen 1,2-dimethylhydrazine. Rats fed fresh vegetables were also injected with a low dose of carcinogen 18-24 h prior to termination. Groups fed lyophilized vegetables did not differ in aberrant crypt foci (ACF), sialomucin-producing foci, or mucin-depleted foci (MDF) numbers. However, all fresh vegetable diets significantly decreased ACF (approximately 40%) and MDF numbers. Activities of the hepatic phase I enzyme CYP2E1 did not differ among groups in either experiment. Hepatic glutathione S-transferase (GST) and quinone reductase activities did not differ among groups fed fresh vegetables, whereas the lyophilized cabbage diets decreased GST activity compared with the basal diet. Groups did not differ in apoptosis and cell proliferation labeling indices in colonic mucosa. This study indicates that fresh but not lyophilized cruciferous vegetables reduce colon cancer risk in rats. These results do not support changes in hepatic carcinogen metabolism or colonic crypt cytokinetics as a mechanism.
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PMID:Cruciferous vegetables reduce morphological markers of colon cancer risk in dimethylhydrazine-treated rats. 1828 61

Colon cancer is the third most malignant neoplasm in the world and it remains today an important cause of death, especially in western countries. In this study, we have evaluated the chemopreventive efficacy of morin on tissue lipid peroxidation and antioxidant status, which are used as biomarkers in 1,2-dimethylhydrazine-induced colon carcinogenesis in a rat model. Male Wistar rats were divided into four groups and received high fat diet. Group 1 served as control, groups 2 and 4 were given a daily treatment of morin (50 mg/kg body weight) orally, everyday for a total period of 30 weeks. Groups 3 and 4 were given weekly subcutaneous injections of DMH at a dose of 20 mg/kg body weight in the groin for 15 weeks. Animals were sacrificed at the end of 30 weeks. The liver, intestine, colon and caecum from different groups were subjected to histopathological studies, determination of lipid peroxidation and antioxidant status. Our results showed decreased levels of liver enzymic and non-enzymic antioxidants and increased levels of lipid peroxidation (LPO) products such as tissue thiobarbituricacid substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD) in DMH treated rats, which were significantly (P < 0.05) reversed on morin supplementation. Moreover, intestinal, colonic and caecal TBARS, LOOH, CD and also the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and reduced glutathione (GSH) were significantly diminished in DMH treated rats, which were significantly (P < 0.05) elevated on simultaneous morin supplementation. Moreover, enhanced activity of intestinal, colonic and caecal ascorbic acid and alpha-tocopherol levels were also observed in DMH alone treated rats, which were significantly (P < 0.05) reduced on morin supplementation. These results indicate that morin could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.
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PMID:Effect of morin on tissue lipid peroxidation and antioxidant status in 1, 2-dimethylhydrazine induced experimental colon carcinogenesis. 1849 50

The role of nonsteroidal anti-inflammatory drugs (NSAIDs) was studied on the antioxidant defense system and nitric oxide-derived damage in a 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Early precancerous lesions were established in the proximal and distal regions of the colon by morphological and histopathological examinations that were greatly regressed by the simultaneous treatment of the three NSAIDs, such as aspirin, celecoxib, and etoricoxib, along with the procarcinogen DMH. The intestinal brush border membrane (BBM) was isolated from the two regions and the colon-specific marker enzyme cysteine-sensitive alkaline phosphatase was assayed, which showed considerable elevation by DMH but reverted back to normal level by all the three NSAIDs. DMH also caused a higher level of lipid peroxidation as measured by malonyldialdehyde production, which was also found to be corrected by the NSAIDs, in both the region of the colonic tissue. The antioxidant activities were further established by a higher level of superoxide dismutase, catalase, glutathione reductase, and glutathione S-transferase in the NSAID treatment as compared to the DMH. The nonenzyme tripeptide, glutathione content was also recovered similarly as an antioxidant defense mechanism. To elucidate whether nitric oxide (NO) also plays an important role in the pathophysiology of colon cancer, the NO and citrulline levels were measured. The results show that the NO was lowered in DMH treatment and elevated by the administration of the NSAIDs while the citrulline level could not be recovered back. The findings of the present investigation indicate the chemopreventive modalities of the NSAIDs, particularly the COX-2 inhibitors.
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PMID:Antioxidative effects of nonsteroidal anti-inflammatory drugs during the initiation stages of experimental colon carcinogenesis in rats. 1854 Aug 45

Colon cancer is still one of the leading causes of death in USA and is increasing at an alarming rate in Asia. It is one of the major causes of death in industrialized countries, and its etiology is known to be a combination of hereditary, environmental, dietary factors and lack of physical activity. Chemoprevention plays a potential role in colorectal cancer. The present study was performed to evaluate the efficacy of hesperetin supplementation on colonic aberrant crypt foci, lipid peroxidation and antioxidant defense system in 1,2-dimethylhydrazine (DMH) induced colon carcinogenesis in male Wistar rats. The rats were segregated into six groups viz., group 1, control rats received modified pellet diet; group 2 rats received modified pellet diet along with hesperetin (30 mg/kg body weight/day); groups 3-6 administrated DMH (20 mg/kg body weight) subcutaneous injection once a week for the first 4 weeks; in addition groups 4-6 received hesperetin at three different doses of 10, 20 and 30 mg/kg body weight/day for 16 weeks. All the rats were sacrificed at the end of the experimental period of 16 weeks. Increased tumor incidence and increased number aberrant crypt foci (ACF) accompanied by a decrease in the tissue lipid peroxidation, glutathione S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities were observed in DMH-treated rats. Administration of hesperetin to DMH treated rats significantly decreased the tumor incidence, the number of aberrant crypt foci with simultaneous enhancement of tissue lipid peroxidation, GST, GPx, SOD, and CAT activities. The results of this study suggest that hesperetin at a dose of 20 mg/kg body weight showed a significant beneficial effect against chemically induced colonic carcinogenesis in rats as compared to the other two doses.
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PMID:Hesperetin exerts dose dependent chemopreventive effect against 1,2-dimethyl hydrazine induced rat colon carcinogenesis. 1864 48

Thiazolides are a novel class of broad-spectrum anti-infective drugs with promising in vitro and in vivo activities against intracellular and extracellular protozoan parasites. The nitrothiazole-analogue nitazoxanide (NTZ; 2-acetolyloxy-N-(5-nitro 2-thiazolyl) benzamide) represents the thiazolide parent compound, and a number of bromo- and carboxy-derivatives with differing activities have been synthesized. Here we report that NTZ and the bromo-thiazolide RM4819, but not the carboxy-thiazolide RM4825, inhibited proliferation of the colon cancer cell line Caco2 and nontransformed human foreskin fibroblasts (HFF) at or below concentrations the compounds normally exhibit anti-parasitic activity. Thiazolides induced typical signs of apoptosis, such as nuclear condensation, DNA fragmentation and phosphatidylserine exposure. Interestingly, the apoptosis-inducing effect of thiazolides appeared to be cell cycle-dependent and induction of cell cycle arrest substantially inhibited the cell death-inducing activity of these compounds. Using affinity chromatography and mass spectrometry glutathione-S-transferase P1 (GSTP1) from the GST class Pi was identified as a major thiazolide-binding protein. GSTP1 expression was more than 10 times higher in the thiazolide-sensitive Caco2 cells than in the less sensitive HFF cells. The enzymatic activity of recombinant GSTP1 was strongly inhibited by thiazolides. Silencing of GSTP1 using siRNA rendered cells insensitive to RM4819, while overexpression of GSTP1 increased sensitivity to RM4819-induced cell death. Thiazolides may thus represent an interesting novel class of future cancer therapeutics.
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PMID:Thiazolides inhibit growth and induce glutathione-S-transferase Pi (GSTP1)-dependent cell death in human colon cancer cells. 1868 61

Dietary fibres are indigestible food ingredients that reach the colon and are then fermented by colonic bacteria, resulting mainly in the formation of short-chain fatty acids (SCFA) such as acetate, propionate, and butyrate. Those SCFA, especially butyrate, are recognised for their potential to act on secondary chemoprevention by slowing growth and activating apoptosis in colon cancer cells. Additionally, SCFA can also act on primary prevention by activation of different drug metabolising enzymes. This can reduce the burden of carcinogens and, therefore, decrease the number of mutations, reducing cancer risk. Activation of GSTs by butyrate has been studied on mRNA, protein, and enzyme activity level by real-time RT-PCR, cDNA microarrays, Western blotting, or photometrical approaches, respectively. Butyrate had differential effects in colon cells of different stages of cancer development. In HT29 tumour cells, e.g., mRNA GSTA4, GSTP1, GSTM2, and GSTT2 were induced. In LT97 adenoma cells, GSTM3, GSTT2, and MGST3 were induced, whereas GSTA2, GSTT2, and catalase (CAT) were elevated in primary colon cells. Colon cells of different stages of carcinogenesis differed in post-transcriptional regulatory mechanisms because butyrate increased protein levels of different GST isoforms and total GST enzyme activity in HT29 cells, whereas in LT97 cells, GST protein levels and activity were slightly reduced. Because butyrate increased histone acetylation and phosphorylation of ERK in HT29 cells, inhibition of histone deacetylases and the influence on MAPK signalling are possible mechanisms of GST activation by butyrate. Functional consequences of this activation include a reduction of DNA damage caused by carcinogens like hydrogen peroxide or 4-hydroxynonenal (HNE) in butyrate-treated colon cells. Treatment of colon cells with the supernatant from an in vitro fermentation of inulin increased GST activity and decreased HNE-induced DNA damage in HT29 cells. Additional animal and human studies are needed to define the exact role of dietary fibre and butyrate in inducing GST activity and reducing the risk of colon cancer.
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PMID:Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. 1938 51

We examined the effects of polysaccharides extracted from Asterina pectinifera on the activities of quinone reductase (QR), glutathione S-transferase (GST), ornithine decarboxylase (ODC), cyclooxygenase (COX)-2 and glutathione (GSH) levels in HT-29 human colon adenocarcinoma cells. We found that the polysaccharides extract induced QR activity in a dose-dependent manner over a concentration range of 20 approximately 60 microg/ml and increased GST activity as much as 1.4-fold over controls. GSH levels were increased 1.3- and 1.5-fold with the extract at 40 and 60 microg/ml, respectively. The activity and protein expression of ODC in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colon cancer cells was inhibited by the extract. The polysaccharides suppressed TPA-induced prostaglandin (PG) production. These data indicate that polysaccharides from A. pectinifera increase phase II detoxification enzyme activity and inhibit ODC and COX-2 activities in HT-29 human colon adenocarcinoma cells. Consequently, this effect may contribute to the protective effect of polysaccharides from A. pectinifera against colon cancer.
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PMID:Chemopreventive effects of polysaccharides extract from Asterina pectinifera on HT-29 human colon adenocarcinoma cells. 1947 Feb 41


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