Antioxidative effects of the spice cardamom against non-melanoma skin cancer by modulating nuclear factor erythroid-2-related factor 2 and NF-κB signalling pathways.

The role of dietary factors in inhibiting or delaying the development of non-melanoma skin cancer (NMSC) has been investigated for many years. Cardamom, which is a dietary phytoproduct, has been commonly used in cuisines for flavour and has numerous health benefits, such as improving digestion and stimulating metabolism and having antitumorigenic effects. We have investigated the efficacy of dietary cardamom against 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin papillomatogenesis in Swiss albino mice that closely resembles human NMSC. Mice were grouped into normal wild type (untreated), vehicle-treated (acetone), carcinogen-treated (DMBA), and DMBA and cardamom-treated (DMBA+CARD) to delineate the role of cardamom against DMBA-induced papillomatogenesis. Oral administration of cardamom to DMBA-treated mice up-regulated the phase II detoxification enzymes, such as glutathione-S-transferase and glutathione peroxidase, probably via activation of nuclear factor erythroid-2-related factor 2 transcription factor in 'DMBA+CARD' mice. Furthermore, reduced glutathione, glutathione reductase, superoxide dismutase and catalase were also up-regulated by cardamom in the same 'DMBA+CARD' group of mice compared with DMBA-treated mice. Cardamom ingestion in DMBA-treated mice blocked NF-κB activation and down-regulated cyclo-oxygenase-2 expression. As a consequence, both the size and the number of skin papillomas generated on the skin due to the DMBA treatment were reduced in the 'DMBA+CARD' group. Thus, the results from the present study suggest that cardamom has a potential to become a pivotal chemopreventive agent to prevent papillomagenesis on the skin.

Chemopreventive potential of diallylsulfide, lycopene and theaflavin during chemically induced colon carcinogenesis in rat colon through modulation of cyclooxygenase-2 and inducible nitric oxide synthase pathways.

Chemoprevention of colorectal cancer has become essential in the modern industrialized world as cancer of the large bowel has become one of the major causes of cancer mortality, second only to lung cancer. Colon cancer integrates lifestyle factors and multistep genetic alterations, and without preventive intervention, a substantial part of the population is likely to develop colorectal cancer at some point during their lives. Diet and nutrition clearly play a role in the etiology of colon cancer. Inhibitory activity of aqueous suspensions of garlic, tomato and black tea was tested on azoxymethane-induced colon carcinogenesis in Sprague-Dawley rats during earlier studies. In the present study, the protective activity of diallylsulfide and lycopene and theaflavin, important antioxidative ingredients of garlic, tomato and black tea, respectively, was assessed during colon carcinogenesis. The effect was observed on aberrant crypt foci, the preneoplastic lesion. As inhibition of cyclooxygenase-2 and inducible nitric oxide synthase activities is correlated with the prevention of colon cancer, the study continues with the determination of the change in the expression of these proteins. Following treatment, significant reduction in the incidences of aberrant crypt foci (by 43.65% in diallylsulfide, 57.39% in lycopene and 66.08% in theaflavin group) was observed, which was in accordance with the reduced expression of cyclooxygenase-2 and inducible nitric oxide synthase. The effect of the intact source was found to be more pronounced than their components used separately.

Dietary cardamom inhibits the formation of azoxymethane-induced aberrant crypt foci in mice and reduces COX-2 and iNOS expression in the colon.

Recently, considerable attention has been focused on identifying naturally occurring chemopreventive compounds capable of inhibiting, retarding, or reversing the multi-step carcinogenesis. The primary aim of the present study was to identify the effects of a commonly consumed spice, viz., cardamom against azoxymethane (AOM) induced colonic aberrant crypt foci (ACF) in Swiss Albino mice. The secondary aim, was to explore the ability of cardamom to modulate the status of proliferation and apoptosis, and to understand its role in altering cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Male Swiss albino mice were injected with AOM (dose: 5mg/Kg body weight) or saline (Group 1) weekly once for two weeks. The AOM-injected mice were randomly assigned to two groups (Groups 2 and 3). While all the groups were on standard lab chow, Group 3 received oral doses of 0.5% cardamom, in aqueous suspension, daily for 8 weeks. Following treatment, significant reduction in the incidences of aberrant crypt foci (p<0.05) was observed. This reduction in ACF was accompanied by suppression of cell proliferation (mean Brdu LI in carcinogen control =13.91+/-3.31, and 0.5% cardamom =2.723+/-0.830) and induction of apoptosis (mean AI in carcinogen control=1.547+/-0.42 and 0.5% cardamom = 6.61+/-0.55). Moreover, reduction of both COX-2 and iNOS expression was also observed. These results suggest that aqueous suspensions of cardamom have protective effects on experimentally induced colon carcinogenesis. Cardamom as a whole and its active components require further attention if the use of this spice is to be recommended for cancer prevention.

Inhibition of azoxymethane-induced aberrant crypt foci in rat by diphenylmethyl selenocyanate through downregulation of COX-2 and modulation of glutathione-S-transferase and lipid peroxidation.

Preventive intervention of colorectal cancer has become essential, as a major portion of the population could develop the disease at some point during their lives. An inverse association between dietary intake of selenium, an important biological trace element, and colorectal cancer risk has been observed through epidemiological and experimental studies. Inhibitory activity of an organoselenocyanate, diphenylmethylselenocyanate, was tested on azoxymethane (15 mg/kg body wt) induced colon carcinogenesis in Sprague-Dawley rats. Pretreatment and concomitant treatment, at a dose of 2 mg/kg body wt, was carried out and the effect was observed on aberrant crypt foci, the preneoplastic lesion. To investigate the mechanism of action of the compound, lipid peroxidation level and glutathione-S-transferase (GST) activities were assessed in the liver as well as in the colon. Expression of cyclooxygenase-2 protein, inducible during colon carcinogenesis, was also analyzed in the colon. Inhibitory activity of the compound was shown by the reduced incidences of aberrant crypt foci in the treated groups (by 63.3%, p=0.00044 in the pretreated group, and by 44%, p=0.0067 in the concomitant treatment group). Significant induction of GST activities and significant reduction in lipid peroxidation level both in the liver as well as in the colon and suppression of cyclooxygenase-2 expression in the colon of the treated groups suggest that the compound could exert its preventive effect at different levels of the carcinogenic process. The preventive effect was better in the pretreatment group than in the concomitant treatment group, suggesting some added protection to the target tissue resulting from preadministration of the compound.

Modulatory influence of garlic and tomato on cyclooxygenase-2 activity, cell proliferation and apoptosis during azoxymethane induced colon carcinogenesis in rat.

Preventive intervention of colorectal cancer has become essential as a major portion of the population may develop the disease at some points during their lives. Diet and nutrition play an important role during this multistep colon carcinogenic process. Inhibitory activity of aqueous suspensions of garlic and tomato, individually and in combination, were tested on azoxymethane induced colon carcinogenesis in Sprague-Dawley rats. The effect was observed on aberrant crypt foci (ACF), the preneoplastic lesion. To investigate the mechanism of action of the agents used, cell proliferation and the level of apoptosis were determined and the expression of cyclooxygenase-2 (COX-2) protein was analyzed in the colon. Following treatment, significant inhibition of the level of cell proliferation (P<0.01 in garlic; P<0.001 in tomato and P<0.001 in combination treatment group with respect to the carcinogen control group), significant induction of apoptosis (P<0.01 in garlic treated; P<0.01 in tomato treated and P<0.001 in combination treatment group with respect to the carcinogen control group) and suppression of COX-2 expression among the treated groups resulted in significant reduction in the incidences of ACF (by 45.27% in garlic, 68.24% in tomato and 71.62% in combination treatment group). The preventive effect was better when the combination of garlic and tomato was administered in comparison to the individual treatment groups, suggesting the synergistic action of garlic and tomato.

Allium vegetables in cancer prevention: an overview.

The Allium genus includes approximately 500 species. Commonly used allium vegetables include garlic, onion, leeks, chives, scallions which are used all over the world in different delicacies. Some allium vegetables have been employed for millenia in the traditional medical practice to treat cardiovascular diseases. They have been shown to have applications as antimicrobial, antithrombotic, antitumor, hypolipidaemic, antiarthritic and hypoglycemic agents. In recent years, extensive research has focused on the anticarcinogenic potential of allium vegetables and their constituents, viz., allylsulfides and flavonoids (particularly quercetin which is present abundantly in onion). Epidemiological studies have shown that higher intake of allium products is associated with reduced risk of several types of cancers. These epidemiological findings are well correlated with laboratory investigations. Organosulfur compounds present in Allium vegetables, are considered to be responsible for the beneficial effects of these herbs. Several mechanisms have been proposed to explain the cancer-preventive effects of Allium vegetables and related organosulfur compounds. These include inhibition of mutagenesis, modulation of enzyme activities, inhibition of DNA adduct formation, free-radical scavenging, and effects on cell proliferation and tumor growth. Although there is a large body of evidence supporting these mechanisms, they are still speculative, and further research is needed to support causality between such properties and cancer-preventive activity in experimental animals. This article reviews current knowledge concerning allium vegetables and cancer prevention.

Indian food ingredients and cancer prevention - an experimental evaluation of anticarcinogenic effects of garlic in rat colon.

The major food items of Indian cuisine include rice, wheat, diary products, and abundant fruits and vegetables. Beside these, there are several kinds of herbs and spices as important ingredients, containing many phytochemicals with medicinal properties, adding taste to Indian cuisine. An impressive body of data exists in support of the concept that Indian food ingredients can be used in preventive strategies aimed at reducing the incidence and mortality of different types of cancers because of their antioxidative, antimutagenic and anticarcinogenic properties. Vital ingredients used in Indian cooking include turmeric, cloves, ginger, aniseed, mustard, saffron, cardamom and garlic Garlic is an indispensable ingredient of Indian food and this report concerns the chemopreventive efficacy of garlic in an azoxymethane induced rodent colon carcinogenesis model. The effect of garlic was evaluated in terms of aberrant crypt foci, putative preneoplastic lesions in the colon. In addition, cell proliferation and levels of apoptosis were determined and the expression of cyclooxygenase-2 protein was analyzed. Following treatment, significant inhibition of cell proliferation and induction of apoptosis, as well as suppression of cyclooxygenase-2 activity were observed, associated with significant reduction in the incidence of aberrant crypt foci. The study points to combined protective effects of garlic components on colon carcinogenesis.

Inhibition of lipid peroxidation and enhancement of GST activity by cardamom and cinnamon during chemically induced colon carcinogenesis in Swiss albino mice.

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.

Inhibition of Cell Proliferation and Induction of Apoptosis During Azoxymethane Induced Colon Carcinogenesis by Black Tea.

Tea (Camellia sinensis) is one of the most popular beverages, consumed worldwide. The health promoting properties of tea have been attributed to its antioxidative polyphenolic constituents and their oxidative products. The aim of the present study was to evaluate the chemopreventive efficacy of a black tea infusion on azoxymethane induced colonic preneoplastic lesions, the aberrant crypt foci in Sprague-Dawley rats. Rats were injected with azoxymethane (15mg/kg.b.w.) and received oral administration of 1% and 2% (w/v) tea infusions from the 1(st)day of carcinogen application. The treatment was continued for 12 weeks. The colons were then assessed for aberrant crypt foci and compared with the untreated carcinogen control group. In situ cell proliferation and in situ apoptosis were also estimated using Brdu incorporation and the TUNEL method, respectively. Aberrant crypt foci were reduced significantly (by 44% in the 1% tea-treated and by about 40% in 2% tea-treated group). Significant decrease in proliferation and increase in apoptosis suggest a possible interplay between the two processes resulting in inhibition of colon carcinogenesis by black tea.