Rhynchophylline attenuates migraine in trigeminal nucleus caudalis in nitroglycerin-induced rat model by inhibiting MAPK/NF-кB signaling

Cis-diamminedichloroplatinum(II) (cisplatin) (CP) is an important chemotherapeutic agent used in the treatment of several cancers. However, it has several side effects including nephrotoxicity gonadotoxicity, hepatotoxicity, and ototoxicity. In in vitro experiments, antioxidants or reactive oxygen species scavengers have a cytoprotective effect on cells exposed to cisplatin (CP). Ellagic acid (EA) is one such bioactive polyphenol that is abundant in some fruits, nuts, and seeds. Various authors have reported that EA has strong antioxidant and antitumor potential. The present study was, therefore, carried out to explore the protective potential of EA on CP-induced gonadotoxicity and nephrotoxicity in colon tumor-bearing mice. Animals were divided into five groups: Group I: normal control, Group II: DMH treated. After 20 weeks of DMH treatment, the animals were divided into four subgroups, viz., Group III: no treatment, Group IV: EA, Group V: CP, and Group VI: CP?+?EA. Administration of EA significantly ameliorated the toxicity caused by CP as indicated by improved kidney function tests and reproductive function tests. EA treatment to CP-abused mice also led to a marked reduction in the extent of peroxidative damage to tissue as was evident from the improvement in the histopathological changes in kidney and testis. Blood counts were also improved on administration of EA to CP-treated mice. This article provides the evidence that antioxidant efficacy of EA has beneficial effects on CP-induced nephrotoxicity and gonadotoxicity and contributes to understanding the role of oxidative stress, and suggests several points as part of the mechanism of CP toxicity.

     

Lupeol and its ester inhibit alteration of myocardial permeability in cyclophosphamide administered rats

Cyclophosphamide (CP), an alkylating agent widely used in cancer chemotherapy causes cardiac membrane damage. Lupeol, a pentacyclic triterpene, isolated from Crataeva nurvala stem bark and its ester, lupeol linoleate possess a wide range of medicinal properties. The effect of lupeol and its ester was evaluated in CP induced alterations in cardiac electrolytes in rats. Male albino rats of Wistar strain were categorized into 6 groups. Group I served as control. Rats in groups II, V and VI were injected intraperitoneally with a single dose of CP (200 mg/kg body weight) dissolved in saline. CP treated groups V and VI received lupeol and lupeol linoleate (50 mg/kg body weight) respectively, dissolved in olive oil for 10 days by oral gavage. At the end of the experimental period, urinary risk factors, activities of ATPases and electrolytes were measured using standard procedures. CP administered rats showed a significant decrease (P < 0.001) in the activities of ATPases. It was associated with significant alterations (P < 0.001) of electrolytes both in serum and cardiac tissue. The levels of urea, uric acid and creatinine were also significantly (P < 0.001) altered in the serum and urine. Lupeol and its ester showed reversal of the above alterations induced by CP. These findings demonstrate that the supplementation with lupeol and its ester could preserve membrane permeability, highlighting their protective effect against CP induced cardiotoxicity.     

Effects of low copper intake on dimethylhydrazine-induced colon cancer in rats.

Rats fed low copper show a high incidence of dimethylhydrazine (DMH)-induced colon tumors compared with rats fed very high Cu. The difference could be due to Cu deficiency in the low group or to Cu toxicity in the high group. In the present study, rats fed low Cu (0.2 ppm) showed greater DMH-stimulated colon tumorigenesis than rats fed adequate Cu (8 ppm). Differences were seen in the number of rats developing tumors (5 of 11 vs 1 of 10), total tumors (7 vs 2), and average tumor mass (1.02 g vs 0.29 g). Low Cu intake did not cause any general DMH toxicity as assessed by body weight gain. To prevent Cu deficiency-induced mortality, low Cu feeding was begun in postweanling rats (weight, about 80 g) housed in groups of five to six, rather than individually. This limited the effects of low Cu feeding to only a moderate Cu deficiency based on several parameters, including three Cu antioxidant enzyme activities. Group-housed rats fed marginal Cu levels (2.5 ppm) showed normal Cu status, and DMH produced only one tumor in 10 rats. In conclusion, high DMH-induced colon tumorigenesis can be found in rats with low activities of Cu antioxidant enzymes.     

Antiproliferative and apoptotic-inducing potential of ellagic acid against 1,2-dimethyl hydrazine-induced colon tumorigenesis in Wistar rats

Colon cancer remains one of the major worldwide causes of cancer-related morbidity and mortality in Western countries and is increasingly common in Asia. Ellagic acid (EA), a major component of polyphenol possesses attractive remedial features. The aim of this study is to divulge the potential effect of EA during 1,2-dimethyl hydrazine (DMH)-induced colon cancer in male Wistar albino rats. The rats were segregated into four groups: group I, control rats; group II, rats received EA (60 mg/kg b.wt./day, orally); rats in group III, induced with DMH (20 mg/kg b.wt.) subcutaneously for 15 weeks; DMH-induced group IV rats were initiated with EA treatment. Colon of the rats treated with DMH exhibited higher glycoconjugates and proliferation index such as elevated expressions of argyrophilic nucleolar organizing regions (AgNORs), proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metalloproteins (MMP-2 and -9), and mast cells. DMH induction also increased phase I-metabolizing enzymes with simultaneous decrease in the phase II detoxifying enzymes. In contrast, dietary administration of EA significantly (p < 0.05) down regulated the proliferation index and restored back the levels of biotransformation enzymes. The carcinogenic insult also altered the expression of pro-apoptotic protein p53, whereas dietary EA administration significantly (p < 0.01) up regulates p53 expression to further induce apoptotic pathway. Ultrastructural changes in colon were also in accord with the above aberrations. Overall findings suggested that the suppression of colon cancer by EA in vivo involves inhibition of cell proliferation, activation of apoptosis, and efficient detoxification.     

Apparent synergism between radiation and the carcinogen 1,2-dimethylhydrazine in the induction of colonic tumors in rats

We have evaluated the interaction of radiation and 1,2-dimethylhydrazine (DMH) with respect to colon carcinogenesis in the Fischer 344 rat and have demonstrated the utility of this model for future more detailed mechanistic studies. In initial experiments, single doses of abdomen-only radiation (9 Gy) or DMH (150 mg/kg) were employed alone or in combination. Radiation was administered 3.5 days prior to the DMH. At 8 months post-treatment, the incidence of DMH-induced colon tumors was doubled by prior radiation exposure. When the protocol was repeated employing a DMH dose of 135 mg/kg with a 6-month observation period, the incidence of tumors induced by DMH alone was reduced, but the combination of radiation plus DMH still resulted in an augmentation of tumor incidence. When the protocol of radiation plus DMH was repeated three times at monthly intervals, a 15-fold increase in tumor incidence (from 5 to 74%) was observed at 6 months post-treatment. This finding demonstrates an apparent synergy between the radiation and the chemical carcinogen. Throughout these studies, the appearance of carcinomas was associated with preexisting colonic lymphoid nodules. The reproducibility of tumor induction as well as range of tumor incidence generated by variations in this system may be adequately sensitive to examine the combination of much lower doses of radiation and/or chemical carcinogen. The relationship between existing lymphoid aggregates which alter local epithelial cell kinetics and which are associated with fenestrations in the basement membrane, and the development of colon cancer in congruent sites may assist in defining dose-response curves for combined agents as well as providing a system for evaluating the mechanisms underlying their interactions.     

Protective role of luteolin in 1,2-dimethylhydrazine induced experimental colon carcinogenesis

The aim of the present study was to unravel the chemopreventive effect of luteolin on bacterial enzymes such as beta-glucuronidase and mucinase in a colon carcinogenesis model induced by 1, 2-dimethyl hydrazine (DMH). Twenty mg/kg body weight of DMH were administered subcutaneously once a week for the first 15 weeks and then discontinued. Luteolin (0.1, 0.2, or 0.3 mg/kg body weight/everyday (p.o.) was administered in a dose dependent manner at the initiation and also at the post-initiation stages of carcinogenesis to DMH treated rats. The animals were sacrificed at the end of 30 weeks. Colon cancer incidence and the activities of bacterial enzymes beta-glucuronidase (in the proximal colon, distal colon, intestines, liver and colon contents) and mucinase (colon and fecal contents) were significantly increased in DMH -treated rats compared to the control rats. On luteolin administration, colon cancer incidence, number of tumors per rat and the activities of beta-glucuronidase and mucinase, were significantly decreased both in the initiation and post-initiation stages of colon carcinogenesis dependent on the three different doses given. The increase in beta-glucuronidase activity may augment the hydrolysis of glucuronide conjugates, liberating toxins, while the increase in the mucinase activity may enhance the hydrolysis of the protective mucins in the colon. Thus our results demonstrate for the first time that luteolin, a dietary flavonoid, exerts chemopreventive and anticarcinogenic effects against DMH induced colon cancer.     

Influence of dietary fiber from coconut kernel (Cocos nucifera) on the 1,2-dimethylhydrazine-induced lipid peroxidation in rats

The influence of dietary fiber from coconut kernel isolated by the neutral detergent fiber method on the antioxidant status in rats treated with the colon specific carcinogen 1,2-dimethylhydrazine (DMH) was studied in rats fed a high-fat diet for 15 weeks. The DMH-treated fiber group showed higher levels of lipid peroxides than the control group treated with DMH at the preneoplastic and neoplastic stages. Free fatty acid levels were found to decrease significantly in the DMH-treated control group, whereas it was near normal in the fiber groups. Superoxide dismutase and catalase activity also were found to be increased in the liver, intestine, proximal colon, and distal colon. Glutathione levels in all the tissues studied showed significant decreases in the fiber group. The results suggest that coconut kernel fiber can protect cells from loss of oxidative capacity with the administration of the procarcinogen DMH.     

Protective effect of ellagic acid on t-butyl hydroperoxide induced lipid peroxidation in isolated rat hepatocytes

Ellagic acid, a plant polyphenol, showed protective effect on isolated rat hepatocytes against destruction due to lipid peroxide formation induced by t-butyl hydroperoxide in vitro. Ellagic acid inhibited the generation of superoxide anions and hydroxyl radicals both in enzymic and non enzymic systems, thus providing protection against oxidative damage.     

Changes in the epithelial permeability of the large intestine of mice in the process of carcinogenesis

1,2-dimethylhydrazine (DMH), a colon carcinogen, being injected weekly to BALB/c mice, inhibits an active sodium transport, increases the transepithelial passive ion permeation and decreases ion selectivity in the descending colon. A single DMH injection leads to the same alterations, manifested for a month, followed by normalization of all the parameters to the control value. Distinctive, wavy changes in electrophysiological parameters were noted after a single injection of "non-colon" carcinogen 7,12-dimethyl-benz(alpha)antracen. It is supposed that the prolonged drop in active sodium transport, transepithelial resistance and ion selectivity are specific reactions of the colonic epithelium to carcinogenic treatment with DMH.     

Attenuation of cyclophosphamide induced toxicity by squalene in experimental rats

Cyclophosphamide (CP) is a widely used antineoplastic drug, which could cause toxicity of the normal cells due to its toxic metabolites. In this study, the protective role of squalene (SQ) towards the tissue defense system in the toxicity induced by CP (150 mg/kg b.w., twice, in 2 consecutive days) was studied in the experimental rats. The significant (P < 0.05) alterations in the levels of enzymic [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)] and non-enzymic antioxidants [total reduced glutathione (GSH), Vitamin E (Vit.E), Vitamin C (Vit.C) and ceruloplasmin] of the heart, red blood cell (RBC) hemolysate and plasma were investigated in the CP toxicity. Alterations in the levels of thiobarbutric acid reactive substance (TBARS) in heart, RBC hemolysate and plasma were also observed as a measure of lipid peroxidation (LPO). These pathological alterations due to CP administration were attenuated by the oral treatment of SQ at a dose of 0.4 ml/day/rat. These observations demonstrate the protective role of SQ towards the tissue defense system of the rats in the CP induced toxicity.     

Multivitamin and mineral supplementation in 1,2-dimethylhydrazine induced experimental colon carcinogenesis and evaluation of free radical status, antioxidant potential, and incidence of ACF

This study was performed to determine the chemopreventive and antioxidant status of multivitamin and mineral (0.01% in drinking water, ad libitum) supplements in 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis. Experimental colon carcinogenesis was induced in male albino Wistar rats by injecting DMH (20 mg·(kg body mass)(-1)) once weekly for 15 consecutive weeks, and administering a multivitamin supplement in 3 regimes (initiation, post-initiation, and entire experimental period) for 32 weeks. We studied lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes) in the circulation and in the tissues, antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and non-enzymatic antioxidant-reduced glutathione) of the tissues, aberrant crypt foci (ACF), and histopathological alterations. DMH-induced rats had an increase in lipid peroxidation products and a lower antioxidant status compared with control animals. Multivitamin and mineral supplementation during the initiation, post-initiation, and the entire study period significantly decreased the levels of lipid peroxidation products in circulation and colonic tissues, significantly elevated the activities of the antioxidant enzymes and reduced glutathione to near normalcy in DMH-induced rats. The incidence of ACF was reduced by [corrected] 84.1% in rats supplemented with multivitamin and minerals for the entire study and prevented the colonic tissue from histopathological alterations induced by DMH.     

Effects of 2.45-GHz microwave radiation and phorbol ester 12-O-tetradecanoylphorbol-13-acetate on dimethylhydrazine-induced colon cancer in mice

The purpose of this study was to investigate the effects of 2.45 GHz microwave (MW) radiation on dimethylhydrazine (DMH)-induced colon cancer in mice. The subjects were 115 Balb/c mice 4 weeks of age. The animals were divided into group A (control), group B (DMH), group C (DMH + MW), and group D [DMH + 12-O-tetradecanoylphorbol-13-acetate (TPA)]. Radiation (10 mW/cm²) was delivered dorsally with the E field parallel to the mouse's long body axis in an anechoic chamber. Radiations were administered 3 hr daily, 6 days per week, over a period of 5 months. The average SAR was estimated to be 10–12 W/kg. During the course of radiation treatments, DMH was injected once per week. The tumor promoter TPA was administered once per week for 10 weeks, from the third week on, after the initial treatment. The incidence of tumors did not significantly differ between the three test groups (groups B, C, and D; P > 0.25). However, the number of tumors, the size of the tumors, and the incidence of protuberant and infiltrative types in tumor-bearing animals were higher in group D compared to groups B and C (P < 0.05). No difference was found between groups B and C (P > 0.25). The study indicates that 2.45 GHz microwave radiation at 10 mW/cm² power density did not promote DMH-induced colon cancers in young mice. The study also showed that TPA could accelerate colon tumor production if a tumor was initiated. © 1994 Wiley-Liss, Inc.     

Inhibition of the Na+,K(+)-ATPase pump during induction of experimental colon cancer.

During the development of large bowel cancer alterations in colonic epithelial ion transport have been observed some of which result in altered intracellular ionic composition. In many tumors intracellular sodium and potassium become elevated and depressed, respectively. This observation suggests that mechanisms governing intracellular homeostasis for sodium and potassium are no longer tightly regulated. Changes in cell membrane permeability, sodium, potassium-ATPase K(+)-ATPase) pump activity, or both may be responsible for these alterations. It is not known when during initiation and development of cancer such changes may occur. To assess whether there are changes in the Na+, K(+)-ATPase pump early during the induction of large bowel cancer and prior to any notable histological changes, we measured the kinetics of the Na+, K(+)-pump in distal colonic mucosa of CF1 mice one week following only four weekly injections of the carcinogen 1,2-dimethyhydrazine (DMH). The kinetics of the pump were found to be best described by a model of highly cooperative binding. The VMAX of the pump in premalignant mucosa was lower for both sodium and potassium substrate activation (55-65% of control) with little change in other kinetic parameters. Depression of VMAX could not be attributed to an increased barium blockable potassium conductance of the basolateral membrane. Na+,K(+)-ATPase activity was also decreased by 50% in the distal colon of DMH treated mice, but was not affected in the less cancer susceptible proximal colon. These data demonstrate that alterations occur in the Na+,K(+)-pump in premalignant mucosa months before gross tumors develop, and these changes may partially explain the altered levels of Na+ and K+ in the cytoplasm of pre-malignant and malignant colonocytes.     

Modulatory influence of dietary resveratrol during different phases of 1,2-dimethylhydrazine induced mucosal lipid-peroxidation, antioxidant status and aberrant crypt foci development in rat colon carcinogenesis

To shed light on the association of lipid peroxidation and antioxidant status with the development of aberrant crypt foci (ACF), we studied the modulatory influence of resveratrol, supplemented in three dietary regimens (initiation, post-initiation and entire period) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were administered DMH (20 mg/kg body weight, s.c.) for 15 weeks and were supplemented with resveratrol (8 mg/kg body weight, p.o. everyday) in three dietary regimens. Intestines and colons were analyzed for the levels of diene conjugates (DC), lipid hydroperoxides (LOOHs) and thiobarbituric acid reactive substances (TBARS). Enzymic antioxidants (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPX; glutathione S-transferase, GST; and glutathione reductase, GR) and non-enzymic reserve (reduced glutathione, GSH; ascorbate; and alpha-tocopherol) were also assessed in the intestine and colon. Unsupplemented DMH exposed rats showed significantly decreased levels/activities of tissue DC, LOOHs, TBARS, SOD, CAT, GSH, GR and significantly elevated (P<0.05) GPX, GST, alpha-tocopherol and ascorbate as compared to control rats. Resveratrol supplementation during the entire period of the study resulted in significant (P<0.01) modulation of lipid peroxidation markers and antioxidants status, which were paralleled with ACF suppression, as compared to DMH-alone treated rats. These results indicate that resveratrol effectively inhibits DMH-induced ACF and colonic tumor development.     

Bile acid induces hydrophobicity-dependent membrane alterations

Elevated concentrations of fecal bile acids are a known risk factor for colon cancer, owing to alterations in cellular signaling. In colonic cells, where bile acid uptake is minimal, the hydrophobicity-induced membrane perturbation and alterations have been proposed, but these membrane alterations are largely uncharacterized. In this study, we examined the determinants and characteristics of bile acid-induced membrane alterations, utilizing PKCalpha activation and cholesterol up-regulation as model indicators. We found that bile acid-induced PKCalpha activation is a function of hydrophobicity and correlated with alteration in membrane lipid composition, as evident by the significant up-regulation in membrane cholesterol and phospholipid. We found that bile acid do not cause cell membrane disruption at a concentration sufficient to activate PKCalpha, but do induce drastic alterations in membrane composition. Bile acid also induced the modification and up-regulation of caveolin-1 in a hydrophobicity-dependent manner, implying widespread receptor dysregulation. Similarly, ERK1/2 activation was observed only in response to hydrophobic bile acids, suggesting hydrophobicity-induced caveolar or membrane stress. Experiments with sodium lauryl sarcosine and cholesteryl hemisuccinate showed that bile acid-induced membrane alterations can be mimicked by hydrophobic molecules unrelated to bile acids, strongly implicating hydrophobicity as an important determinant of bile acid signaling.     

Role of oregano on bacterial enzymes in 1,2-dimethylhydrazine-induced experimental colon carcinogenesis

Colon cancer incidence is higher in developed countries than in developing countries. We determined the effect of oregano (Origanum vulgare L.) on fecal bacterial enzyme activities in 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis in rats. Male Wistar albino rats were divided into 6 groups and all animals were fed with a high-fat diet (20% fat in the diet). Group 1 served as control and group 2 animals received 60 mg.kg(-1) body weight (b.w.) oregano daily for 15 weeks. To induce colon cancer, DMH (20 mg.kg(-1) b.w.) was injected subcutaneously once a week for the first 4 weeks (groups 3-6). In addition, oregano was administered at 20, 40, or 60 mg.kg(-1) b.w. each day orally for the entire 15 weeks (groups 4-6). We analyzed the fecal bacterial enzyme activities and found it to be significantly higher in the group treated with DMH alone than in the control group. Oregano supplementation at all 3 doses significantly suppressed the bacterial enzyme activities and modulated oxidative stress significantly compared with the unsupplemented DMH-treated group. Results of our present investigation therefore revealed that oregano markedly inhibited DMH-induced colon carcinogenesis and that the optimal dose of 40 mg.kg(-1) b.w. was more effective than either the higher or lower doses.     

In vitro DNA and nuclear proteins alkylation by 1,2-dimethylhydrazine

The methylating carcinogen 1,2-dimethylhydrazine (DMH) CAS 540.73.8 is highly organ-specific and, under certain experimental conditions, produces a high incidence of adenocarcinoma in the colon of rodents. We have tried to assess the possibility that part of the organ-specifity in the carcinogenic effect of DMH could be attributed to its metabolism by specific microsomal enzymes. In particular, we compared the in vitro effects of DMH in the presence of either colon or liver microsomes from animals that had been treated with microsomal enzyme inducers. V79 Chinese hamster cells were used as the target to evaluate the damage to the genetic material, as judged by (1) formation of adducts of DNA bases and (2) amino acid modifications in nuclear proteins using [Me-14C]DMH and appropriate analytical detection systems. Our results tend to support the above postulated hypothesis.     

The Effects of Ascorbic Acid and Iron Co-Supplementation on the Proliferation of 3T3 Fibroblasts

Exposure of 3T3 fibroblasts to Fe reveals a concentration-dependent inhibition of cell proliferation compared to control cells, the apparent threshold for this iron-mediated effect being 5 μM Fe^II. The inhibition of cell proliferation was accompanied by an enhancement of total malondialdehyde (MDA) levels (as detected directly by hplc) in the cells at higher iron concentrations. The co-supplementation of Fe with varying concentrations of ascorbic acid over the range 5 μM to 240 μM had no significant effect on the threshold for iron toxicity or lipid peroxidation. These results show that there is neither a significant exacerbation of the pro-oxidant effect of Fe^II nor any protective effect of ascorbate when cultures of 3T3 mouse fibroblasts are exposed to co-supplementation regimes of iron with ascorbic acid.     

Chemoprevention of DMH-induced rat colon carcinoma initiation by combination administration of piroxicam and C-phycocyanin

Cancer research illustrated that combinatorial studies can provide significant improvement in safety and effectiveness over the monotherapy regimens. A combination of two drugs may restrain precancerous colon polyps, opening a new possible opportunity for chemoprevention of colon cancer. In this context, chemopreventive efficacy of a combination regimen of C-phycocyanin, a biliprotein present in Spirulina platensis, a cyanobacterium, which is a selective cycloxygenase-2 (COX-2) inhibitor and piroxicam, a traditional non-steroidal anti-inflammatory drug was considered in 1,2 dimethylhyadrazine (DMH)-induced colon carcinogenesis in rats. Western blotting, immunohistochemistry, DNA fragmentation, fluorescent staining, PGE(2) enzyme immunoassay, and carrageenan-induced paw edema test were performed along with morphological and histological analysis. DMH treatment showed a rich presence of preneoplastic lesions such as multiple plaque lesions, aberrant crypt foci, and well-characterized dysplasia. These features were reduced with piroxicam and C-phycocyanin administration. The number of apoptotic cells was featured prominently in all the groups compared with DMH. DMH treatment revealed intact high molecular weight genomic DNA with no signs of laddering/DNA fragmentation while it was noticeable significantly in control and DMH + piroxicam + C-phycocyanin. DMH group showed highest COX-2 expression and PGE(2) level in comparison with other groups. Doses of piroxicam and C-phycocyanin used in the present study were established at an anti-inflammatory range. A combination regimen of piroxicam and C-phycocyanin, rather than individually has the much greater potential for reduction of DMH-induced colon cancer development and COX-2 being the prime possible target in such chemoprevention.     

Chemopreventive efficacy of green tea drinking against 1,2‐dimethyl hydrazine‐induced rat colon carcinogenesis

Colorectal cancer is one of the leading causes of tumour‐related deaths. In the present study, the chemopreventive effect of green tea on 1,2‐dimethylhydrazine (DMH)‐induced colon carcinogenesis was studied in male Wistar rats. The DMH group received subcutaneous injections of DMH (30 mg kg^?1 body weight) once a week for 30 weeks, the normal group received the vehicle of DMH, and the DMH + green tea group received DMH simultaneously with 1% green tea as their sole source of drinking fluid throughout the experimental period. In the DMH group treated with green tea, significant reductions in gene overexpressions of colonic nuclear factor κB (NF‐κB), tumour necrosis factor α, inducible nitric oxide synthase and cyclooxygenase 2, and NF‐κB immunostaining indicates the anti‐inflammatory effect of green tea in attenuating colon cancer. Moreover, the anti‐angiogenic and anti‐invasiveness effects of green tea were revealed as reductions of both vascular endothelial growth factor and matrix metalloproteinase‐7 mRNA expression levels. These effects were confirmed by the significant reduction of serum tumour necrosis factor α, C‐reactive protein levels, inhibition of tumour incidence, and nearly normal survival rate and colonic architecture. It can be concluded that green tea exerts a potent chemopreventive effect on colon carcinogenesis possibly due to the inhibition of NF‐κB. Copyright © 2012 John Wiley & Sons, Ltd.