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Colorectal carcinoma is one of the utmost diagnosed cancer with a steep increase in mortality rate. The incidence has been increasing in developing countries like India due to a westernization life style. Flavonoids have been explored widely for its various pharmacological activity including antitumor activity. Orientin, an analogue of luteolin (citrus flavonoid) isolated from rooibos and tulsi leaves is also expected to deliver significant antitumor activity similar to that of luteolin. The present study anticipates exploring the antitumor activity of orientin against colorectal carcinoma cells (HT29). Orientin exhibited remarkable cytotoxicity and antiproliferative activity against HT29 cells, which is clearly evident from tetrazolium based cytotoxicity and lactate dehydrogenase release assays. Orientin induce G0/G1 cell cycle arrest and regulates cyclin and cyclin-dependent protein kinases in order to prevent the entry of the cell cycle to the S phase. Annexin V-FITC (V-Fluorescein Isothiocyanate) dual staining reveals the apoptotic induction ability of orientin. The Bcl-2 family proteins along with the inhibitor of apoptotic proteins were regulated and the tumor suppressor p-53 expression have been decreased. In conclusion, our results proposed that orientin could be a potent chemotherapeutic agent against colorectal cancer after ascertaining their molecular mechanisms.

Pelargonidin (PE) is an anticancer anthocyanidin that is abundant in berries. In this study, we found that PE irreversibly inhibits human colorectal adenocarcinoma cells (HT29) at micromolar concentrations in a dose- and time-dependent manner, which was determined using the MTT assay, and the GI50 value was found to be 0.31 μM for a 24 h exposure. Inverted light microscopy observation and AO/EtBr staining of treated HT29 cells showed apoptotic morphological changes such as chromatin condensation and cell shrinkage. In addition, PE treatment showed a DNA ladder pattern, which is the hallmark of typical intrinsic apoptotic characterization by molecular DNA fragmentation analysis in HT29 cells. PE accumulates cells at G2/M of the cell cycle arrest in a dose-dependent manner as determined by flow cytometry analysis of propidium iodide staining. The G2/M phase cell cycle arrest peak of DNA, characteristic of apoptosis, was observed in the PE-treated cells. In addition, treatment with PE caused the release of cytochrome c from mitochondria into the cytosol. Western blotting analysis showed that PE significantly upregulated the activities of caspase-3 and -9 in comparison with a control group; subsequently, cleavage of PARP-1 protein is suggested, whereas PE significantly downregulated the expression of Bcl-2 and Bcl-xL and upregulated the expression of Bax and Bid. Furthermore, the downregulation of CDC25C, cyclin B1, and CDK1 expression resulted in the induction of G2/M cell cycle arrest in the HT29 cells. In contrast, PE induces the expression of p53 and p21waf1 in HT29 cells. Collectively, these results show that PE has anticancer activities against HT29 cells through cell cycle arrest, DNA damage, and activation of the mitochondrial signalling pathway. This might provide a potential therapeutic option in the management of colon adenocarcinoma.

Eriodictyol, one of the strong flavonoids extracted from Eriodictyon californicum, is known for its antioxidant and anticarcinogenic properties. We estimated the chemopreventive effect of eriodictyol on 1,2 dimethylhydrazine (DMH)-induced experimental colon carcinogenesis in male albino Wistar rats. The rats were randomized into six groups. Our results evaluated the effect of eriodictyol supplementation (200 μg per kg b.w.) on DMH (20 mg per kg b.w)-induced rats (Groups 4–6). The incidence of polyps, aberrant crypt foci (ACF) and the lipid peroxidation levels were significantly decreased as compared to those in the DMH-alone treated rats (Group 2). In eriodictyol-supplemented DMH-treated rats, we observed increased activity of enzymatic and non-enzymatic antioxidants in the circulatory system, liver, and colon. The bacterial enzymes activities of mucosa and faecal were significantly decreased in the group with treatment of eriodictyol on DMH-induced rats. Moreover, in the eriodictyol-supplemented DMH-exposed rats, we observed reduced malignant glands of a histopathological appearance in both liver and colon tissue. Furthermore, we also observed reduced AgNORs counts of eriodictyol supplemented to the DMH-exposed rats. Therefore, we can conclude that eriodictyol can be used as an effective chemopreventive agent against DMH-induced colon carcinogenesis in experimental animal models.

Pelargonidin is an anthocyanidin isolated from plant resources. It shows strong cytotoxicity toward various cancer cell lines, even though the carcinogenesis-modulating pathway of pelargonidin is not yet known. One of our previous reports showed that pelargonidin arrests the cell cycle and induces apoptosis in HT29 cells. Flowcytometry and immunoblot analysis confirmed that pelargonidin specifically inhibits the activation of CDK1 and blocks the G2-M transition of the cell cycle. In addition, DNA fragmentation was observed along with induction of cytochrome c release-mediated apoptosis. Hence, the aim of the present study was to investigate the molecular mechanism of pelargonidin's action on cell cycle regulators CDK1, CDK4, and CDK6 as well as the substrate-binding domain of DNMT1 and DNMT3A, which regulate the epigenetic signals related to DNA methylation. The results of docking analysis, binding free energy calculation, and molecular dynamics simulation correlated with the experimental results, and pelargonidin showed a specific interaction with CDK1. In this context, pelargonidin may also inhibit the recognition of DNA and catalytic binding by DNMT1 and DNMT3A. The HOMO-LUMO analysis mapped the functional groups of pelargonidin. Prediction of pharmacological descriptors suggested that pelargonidin can serve as a multitarget inhibitor for cancer treatment.

Objective An attempt has been made to evaluate the mitochondrial protection in acute and chronic periods after isoproterenol (ISO)-induced myocardial-infarction (MI) in male Wistar rats. Materials and methods Luteolin was supplemented by intra-gastric intubation at a daily dose of 0.3 mg/kg body weight for 30 days. In the acute MI model, luteolin had been administered once per day to rat groups during 30 days. On 29th and 30th days, the rats of the acute MI control groups were administered 85 mg/kg body weight, isoproterenol, intra-peritoneally at an interval of 24 h. In the chronic MI model luteolin was supplemented to the rat group during 30 days. On the 1st and 2nd days, the rats of the chronic MI control and luteolin treatment groups were administered ISO by the same way. Results The isoproterenol-treated rats both in acute and chronic models showed an increase in the level of TBARS and a decrease in the activities of mitochondrial antioxidants in MI rats, an increase in levels of mitochondrial lipid profile except phospholipids and the activities of mitochondrial enzymes were decreased in isoproterenol-treated rats. Oral treatments with luteolin in both acute and chronic models showed a significant decrease in the levels of mitochondrial lipid peroxidation, increase in the mitochondrial antioxidant levels and also decrease in the mitochondrial enzymes. Conclusion Thus the present study revealed that luteolin ameliorates mitochondrial damage in isoproterenol induced myocardial infarction by maintaining lipid peroxidation metabolism due to its free radical scavenging, mitochondrial lipids, antioxidants and mitochondrial enzymes. Histopathological observations were also in correlation with the biochemical parameters.

Objectives: This study is designed to evaluate the cardioprotective effect of fenugreek on isoproterenol- induced myocardial infarction and is investigated by an in vivo method in rats. Materials and Methods: Male Wistar albino rats were divided into four groups (n=10). Group I received 0.5% CMC treated as normal control group. Group II received isoproterenol (85 mg/kg body weight) intraperitoneal (i.p.) for two consecutive days (14th and 15th days). Group III received fenugreek (250 mg/kg body weight) intragastric intubation for 15 days. Group IV rats received fenugreek as in Group III and additionally isoproterenol was given for two consecutive days (14th and 15th days). Results: The results described the cardioprotective effect that observed in Group IV showed significantly (P< 0.05) decreased levels of TBARS and enhanced the activities of both enzymatic and non-enzymatic antioxidants (SOD, CAT, GPx and GSH) in myocardial infarcted rats when compared to Groups II and III. Histopathological studies were also co-relating with the above biochemical parameters. Conclusion: These findings concluded the cardioprotective effect of fenugreek on lipid peroxidation and antioxidant defense system during isoproterenol-induced myocardial infarction in rats.

Background: Colon cancer is one of the most common forms of malignant tumors in humans, and its incidence is increasing. Since the intestinal microflora is directly in contact with the colonic cells, the enzymes of the bacterial microflora may also play a role in colon carcinogenesis. We studied the activity of bacterial enzymes in experimental colon cancer. Methods: Twenty milligrams per kilogram body weight of 1,2-dimethyl hydrazine (DMH) was administered subcutaneously once a week for first 15 weeks and then discontinued. Coconut cake (25%) was mixed in the diet and given to 30 rats to study the diet effect throughout the experimental period. After 30 weeks, the macroscopic findings in the colon as well as the incidence of tumors in 30 rats was recorded in each group and the activity of β-glucuronidase and mucinase was estimated in the tissues, colon and fecal contents of 10 rats per group. Results: Average number of tumors in the colon as well as the incidence of cancer was significantly increased in DMH-treated rats which was markedly reduced on supplementing coconut cake. DMH injections significantly elevated both the activities of β-glucuronidase (distal colon, distal intestine, liver and colon contents) and mucinase (colon and fecal contents) as compared to the control rats. The increase in β-glucuronidase activity may augment the hydrolysis of glucuronide conjugates, liberating the toxins, while the increase in mucinase activity may enhance the hydrolysis of the protective mucins in the colon. Coconut cake supplementation to DMH-treated rats significantly decreased the incidence and number of tumors as well as the activity of β-glucuronidase and mucinase. Conclusions: Coconut cake has a protective effect against DMH induced colon cancer by virtue of its ability to lower the activities of the microbial enzymes β-glucuronidase and mucinase.

Previous studies suggest a possible link between leptin and hepatic inflammation; however the role of leptin in liver diseases remains unclear. The purpose of the present study was to evaluate the effect of leptin on plasma and tissue lipids in experimental hepatotoxicity. Administering ethanol (6.32 g/kg body weight) to 4-weekold healthy mice for 45 days resulted in significantly elevated levels of plasma and tissue phospholipids, triglycerides and free fatty acids as compared with those of the control animals. Subsequent to the experimental induction of hepatotoxicity (i.e., the initial period of 30 days) exogenous leptin was simultaneously administered (230 mg/kg body weight) every alternate day for 15 days along with the daily dose of alcohol. Leptin administration to control and alcohol-treated mice reduced the weight gain and significantly lowered the levels of plasma and tissue lipids as compared with the untreated control and alcohol supplemented mice. It is postulated that the increase in systemic leptin levels lower the plasma and tissue lipids of alcohol-treated mice, which operates independently of changes in food intake, body weight and the size of the fat stores.

Colon cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer death in the United States. Ginger, a natural spice having both antioxidant and antimutagenic property, is known to inhibit chemical carcinogenesis. This study was designed to investigate the chemopreventive efficacy of ginger on the activity of bacterial enzymes in rats induced colon cancer by 1,2-dimethylhydrazine. Twenty milligrams per kilogram body weight of 1,2-dimethylhydrazine was administered subcutaneously once a week for the first 15 weeks and then discontinued. Ginger (50 mg/kg body weight/per day, oral) was given at the initiation and also at the postinitiation stages of carcinogenesis to 1,2-dimethylhydrazine-treated rats. The animals were killed at the end of 30 weeks. The macroscopic findings in the colon and the incidence of tumors were recorded in each group, and the activity of beta-glucuronidase and mucinase was estimated in the tissues and fecal contents of rats. After a total experimental period of 32 weeks (including 2 weeks of acclimatization), tumor incidence was 100% in 1,2-dimethylhydrazine-treated rats. The incidence of cancer as well as the number of tumors in the colon was significantly reduced both in the initiation and postinitiation stages of carcinogenesis on ginger administration. The activities of bacterial enzymes beta-glucuronidase (proximal colon, distal colon, intestines, liver and colon contents) and mucinase (colon and fecal contents) were significantly elevated in 1,2-dimethylhydrazine-treated rats as compared with the control rats. The increase in beta-glucuronidase activity may augment the hydrolysis of glucuronide conjugates, liberating the toxins, while the increase in the mucinase activity may enhance the hydrolysis of the protective mucins in the colon. Ginger administration to 1,2-dimethylhydrazine-treated rats significantly decreased the incidence and number of tumors as well as the activity of beta-glucuronidase and mucinase. Thus, ginger has a chemopreventive and anticarcinogenic effect against 1,2-dimethylhydrazine-induced colon cancer by virtue of its ability to lower the activities of the microbial enzymes beta-glucuronidase and mucinase.

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.

Colon cancer is the second most common cancer among men and women worldwide. We investigated the effect of red chilli (Capsicum annum L.), cumin (Cuminum cyminum L.), and black pepper (Piper nigrum L.) on colon cancer induced in rats by a colon-specific carcinogen, 1,2-dimethylhydrazine (DMH). Colon cancer was induced by subcutaneous injection of DMH at a dosage of 20 mg/kg of body weight (15 doses, at 1-week intervals). The rats were continued with the standard pellet diet and supplemented red chilli [C. annum L., 0.015% (wt/wt) mixed with the diet], cumin seeds [C. cyminum L., 1.25% (wt/wt) mixed with the diet], and black pepper (P. nigrum L., 0.5% (wt/wt) mixed with the diet] throughout the experimental period. After the total experimental period of 32 weeks (including 2 weeks of acclimatization) the incidence and number of tumors in the colon were observed to be significantly higher in the rats administered DMH and/or red chillis, as compared with the cumin + DMH and black pepper + DMH groups. No tumors were observed in the control, cumin + DMH, or black pepper + DMH groups. The levels of fecal bile acids and neutral sterols in 24-hour fecal samples were significantly decreased in DMH + chilli-administered rats, while the excretion of fecal bile acids and neutral sterols was significantly increased in cumin + DMH- and black pepper + DMH-administered rats. In DMH-, chilli-, and chilli + DMH-administered rats the levels of cholesterol, cholesterol/phospholipid ratio, and 3-hydroxy-3-methylglutaryl-CoA reductase activity were decreased in cumin + DMH- and black pepper + DMH-treated rats. The phospholipid levels were reduced in the DMH, chilli, and chilli + DMH groups as compared with the cumin + DMH and black pepper + DMH groups. Our results show that chilli supplementation promotes colon carcinogenesis, whereas cumin or black pepper suppresses colon carcinogensis in the presence of the procarcinogen DMH.

We investigated the chemopreventive potential of luteolin on hepatic and circulatory lipid peroxidation and antioxidant status during 1,2-dimethylhydrazine induced colon carcinogenesis in rats. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight for 15 weeks. Luteolin (0.2 mg/kg body weight/everyday p.o.) was given at the initiation and also at the postinitiation stages of carcinogenesis to DMH treated rats. The animals were sacrificed at the end of 30 weeks. Enhanced lipid peroxidation in the liver and circulation of tumor bearing rats was accompanied by a significant decrease in the levels of plasma and hepatic reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), vitamin C, vitamin E and beta-carotene in DMH treated rats as compared to the control rats. Intragastric administration of luteolin (0.2mg/kg body weight) to DMH-treated rats significantly reduced the incidence and size of tumor in the colon, reduced lipid peroxidation levels and enhanced the plasma and hepatic activities of GSH, GPx, GST, GR, SOD, CAT, vitamin C, vitamin E and beta-carotene. Thus the chemopreventive efficacy of luteolin against colon carcinogenesis is evidenced by our preliminary studies which showed decreased incidence of tumors and the antiperoxidative and antioxidant effect of luteolin. Further study on the exact mechanism of action of luteolin in preventing colon carcinogenesis is yet to be elucidated.

Colon cancer is the third most common cancer and second leading cause of cancer-related death in the United States. A number of recent articles demonstrate the importance of natural products as cancer chemopreventive agents. In this study, we evaluated the chemopreventive efficacy of luteolin, a flavonoid, on tissue lipid peroxidation and antioxidant status, which are used as biomarkers in DMH-induced experimental colon carcinogenesis. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight for 15 weeks. Luteolin (0.2 mg/kg body weight/everyday p.o.) was given to the DMH-treated rats at the initiation and post-initiation stages of carcinogenesis. The animals were killed after 30 weeks. After a total experimental period of 32 weeks (including 2 weeks of acclimatization), tumor incidence was 100% in DMH-treated rats. In those DMH-treated rats that had received luteolin during the initiation or post-initiation stages of colon carcinogenesis, the incidence of cancer and the colon tumor size was significantly reduced as compared to that for DMH-treated rats not receiving luteolin. In the presence of DMH, relative to the results for the control rats, there were decreased levels of lipid peroxidation, as denoted by thiobarbituric acid reactive substances (TBARS), conjugated dienes and lipid hydroperoxides, decreased activities of the enzymic antioxidants superoxide dismutase (SOD) and catalase (CAT), and elevated levels of glutathione and the glutathione-dependent enzymes reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR), and of the non-enzymic antioxidants vitamin C and vitamin E. Our study shows that intragastric administration of luteolin inhibits colon carcinogenesis, not only by modulating lipid peroxidation and antioxidant status, but also by preventing DMH-induced histopathological changes. Our results thus indicate that luteolin could act as a potent chemopreventive agent for colon carcinogenesis.

Background Ginger (Zingiber officinale Rosc) is a natural dietary component, which has antioxidant and anticarcinogenic properties. We investigated the effect of ginger on the initiation and post-initiation stages of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Wistar rats. Methods Rats were given a weekly subcutaneous injection of DMH (20 mg/kg body weight) in the groin for 15 weeks. Ginger (50 mg/kg body weight/everyday p.o.) was given to the rats at the initiation, post-initiation stages of carcinogenesis. The activity of lipid peroxidation was studied by measuring the formation of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD), and the antioxidant status by measuring superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST), glutathione reductase (GR), reduced glutathione (GSH), vitamins C, E, and A concentrations in the circulation of 1,2-dimethylhydrazine-induced experimental colon cancer. Results In the presence of a known colon carcinogen, DMH, plasma lipid peroxidation (TBARS, lipid hydroperoxides and conjugated dienes) and cancer incidence were significantly increased whereas enzymic (GPx, GST, GR, SOD and CAT) and non-enzymic antioxidant concentrations (GSH, vitamins C, E, and A) were decreased as compared to control rats. The number of tumors as well as the incidence of cancer was significantly decreased on treatment with ginger. In addition, ginger supplementation at the initiation stage and also at the post-initiation stages of carcinogenesis significantly reduced circulating lipid peroxidation and significantly enhanced the enzymic and non-enzymic antioxidants as compared to unsupplemented DMH-treated rats. Conclusions Ginger supplementation suppresses colon carcinogenesis in the presence of the procarcinogen DMH.

Cervical carcinoma is the second most common cancer worldwide. The extent of free radical induced oxidative stress can be exacerbated by the decreased efficiency of antioxidant defense mechanisms. Low levels of essential antioxidants in the circulation have been found to be associated with an increased risk of cancer. The aim of our study was to assess the extent of oxidative stress, the levels of antioxidants like superoxide dismutase (SOD), catalase (CAT), ceruloplasmin and to evaluate tumor markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and total sialic acid (TSA) levels in circulation of women with cervical carcinoma and to compare our findings with age matched controls. Low levels of SOD and CAT observed in the circulation of cervical cancer patients may be due to their increased utilization to scavenge lipid peroxides as well as sequestration by tumor cells. Higher levels of TSA, AST, ALT and ALP, in the circulation of cervical cancer patients may be used in the diagnosis and treatment monitoring of patients with cervical carcinoma.

Previous studies suggest a possible link between leptin and decreased lipid levels, however, the role of leptin in high-fat diet-induced hyperlipidemia remains unclear. The aim of our study was to evaluate the effect of administering leptin on plasma and tissue lipids in mice fed a high-fat diet. Feeding a high-fat diet (2% cholesterol, 0.125% bile salts, 5% peanut oil) to four-week-old healthy mice for a period of 45 days, resulted in significantly elevated levels of plasma and tissue total cholesterol, phospholipids, free fatty acids and triglycerides as compared with those of the control mice. Subsequently after thirty days, exogenous leptin (230 microg/kg i.p.) was administered simultaneously with the daily dose of high-fat diet every alternate day for fifteen days. Leptin administration significantly reduced the levels of total cholesterol, phospholipids, free fatty acids and triglycerides in the plasma, liver, heart and kidney of both the control and high-fat diet fed mice. Moreover, leptin administration markedly reduced the levels of plasma LDL, VLDL and elevated plasma HDL and the activity of lipoprotein lipase as compared with the untreated control and high-fat diet fed mice. Thus, leptin administration was found to have a marked protective effect against hyperlipidemia and thus obesity, by virtue of its lipid lowering effects.