Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GSTP1 is a member of the glutathione S-transferase enzyme superfamily, which catalyzes the conjugation of electrophiles with glutathione in the process of detoxification. GSTP1 is widely overexpressed in colorectal cancer, from aberrant crypt foci to advanced carcinomas. Increased expression of GSTP1 is associated with multidrug resistance and a worse clinical prognosis. However, GSTP1-null mice have an increased risk of tumor formation. Thus, the biological function of GSTP1 in colorectal cancer biology remains speculative. In an effort to gain further insights into the role of GSTP1 in tumorigenesis, we disrupted the GSTP1 gene in HCT116 human colorectal cancer cells using targeted homologous recombination. We find that loss of GSTP1 resulted in impaired clonogenic survival and proliferation. Specifically, under growth-limiting conditions, (a) GSTP1 protected HCT116 cells from oxidative stress and associated apoptosis and (b) promoted mitogen-activated protein kinase-extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase-mediated G1-S cell cycle progression. In vivo, GSTP1 was critical for engraftment and growth of HCT116 tumor xenografts. These studies directly show that GSTP1 promotes clonogenic survival and proliferation in HCT116 human colon cancer cells.
 ...
PMID:Glutathione S-transferase pi1 promotes tumorigenicity in HCT116 human colon cancer cells. 1623 Apr 13

Artepillin C, a prenylated phenylpropanoid found specifically in Brazilian propolis, has been shown to be a bioavailable antioxidant. In this study, artepillin C was tested for colon cancer-preventing activity using azoxymethane-challenged ddY mice. Oral doses of 80 and 160 mg/kg body weight of propolis or 10mg/kg of artepillin C (equi-amounts to 160 mg propolis) reduced significantly the frequency of colonic aberrant crypt foci (ACF) by 39.2, 43.7 and 43.4%, respectively. In liver of the mice, glutathione S-transferase and NADPH:quinone reductase activity increased with the doses of propolis or artepillin C, and an antioxidant-responsive element (ARE) was found to be activated for binding DNA. Artepillin C is considered to suppress the formation of colonic ACF through the activation of ARE and induction of phase II enzymes in liver.
 ...
PMID:Dietary artepillin C suppresses the formation of aberrant crypt foci induced by azoxymethane in mouse colon. 1623 34

Dietary fibers are fermented by the gut flora to yield short chain fatty acids (SCFAs), which inhibit the growth of tumor cells, induce glutathione S-transferases (GSTs), and protect cells from the genotoxic activity of 4-hydroxynonenal (HNE). Here, we investigated effects of wheat bran-derived arabinoxylans and fermentation products on these parameters of chemoprevention. Newly isolated water extractable (WeAx) and alkali extractable arabinoxylans (AeAx) were fermented under anaerobic conditions with human feces. Resulting fermentation supernatants (FSs) were analyzed for SCFAs and used to treat HT29 colon cancer cells. Cell growth, cytotoxicity, antigenotoxicity against hydrogen peroxide (H2O2) or HNE, and GST activity were determined. Nonfermented WeAx decreased H2O2-induced DNA damage by 64%, thus demonstrating chemoprotective properties by this nonfermented wheat bran fiber. The fermentation of WeAx and AeAx resulted in 3-fold increases of SCFA, but all FSs (including the control without arabinoxylans) inhibited the growth of the HT29 cells, reduced the genotoxicity of HNE, and enhanced the activity of GSTs (FS WeAx, 2-fold; FS AeAx, 1.7-fold; and control FS, 1.4-fold), which detoxify HNE. Thus, increases in SCFAs were not reflected by enhanced functional effects. The conclusion is that fermentation mixtures contain modulatory compounds that arise from the feces and might add to the effectiveness of SCFAs.
 ...
PMID:Both wheat (Triticum aestivum) bran arabinoxylans and gut flora-mediated fermentation products protect human colon cells from genotoxic activities of 4-hydroxynonenal and hydrogen peroxide. 1653 80

Colon cancer is a leading cause of cancer death and its prevention is of great interest throughout the world. This study was conducted to examine the efficacy of different doses of dietary caraway (Carum carvi L.) on tissue lipid peroxidation (LPO) and antioxidant profile in rat colon carcinogenesis. Wistar male rats were divided into 6 groups and were fed a modified pellet diet for the whole of 30 weeks. To induce colon cancer, rats were given a weekly subcutaneous injection of 1,2-dimethylhydrazine (DMH) at a dose of 20 mg kg(-1) (based on body weight) for the first 15 weeks. Caraway was supplemented every day orally at doses of 30, 60 and 90 mg kg(-1) for different groups of rats for the total period of 30 weeks. All rats were sacrificed at the end of 30 weeks, the colons were examined visually for masses and were subsequently evaluated histologically. The results showed diminished levels of intestinal, colonic and caecal LPO products, such as conjugated dienes (CD), lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS) and also the antioxidants superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione reductase (GR) in DMH treated rats, which were significantly reversed (P<0.05) on caraway supplementation. Moreover, enhanced activity of intestinal, colonic and caecal glutathione peroxidase (GPx), glutathione S-transferase (GST) and colonic ascorbic acid and alpha-tocopherol levels were observed in carcinogen-treated rats, which were significantly (P<0.05) reduced on caraway supplementation. Thus, our study showed that caraway supplementation at a dose of 60 mg kg(-1) had a modulatory role on tissue LPO, antioxidant profile and prevented DMH-induced histopathological lesions in colon cancer rats.
 ...
PMID:Dose-response efficacy of caraway (Carum carvi L.) on tissue lipid peroxidation and antioxidant profile in rat colon carcinogenesis. 1687 60

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
 ...
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.
 ...
PMID:Antitumor and cytotoxic effects of Phyllanthus polyphyllus on Ehrlich ascites carcinoma and human cancer cell lines. 1782 93

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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Hesperetin exerts dose dependent chemopreventive effect against 1,2-dimethyl hydrazine induced rat colon carcinogenesis. 1864 48


<< Previous 1 2 3 4 5 6 Next >>