Archana Sengupta

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.

Inhibition of DMBA/croton oil-induced two-stage mouse skin carcinogenesis by diphenylmethyl selenocyanate.

Selenium, an essential micronutrient, is associated with antioxidant functions, physiological defence mechanisms against different diseases including several types of cancers. Search for new selenium compounds with more chemopreventive activities and lesser toxicities are in progress. In the present study, the antioxidative roles of a synthetic organoselenium compound, diphenylmethyl selenocyanate, were evaluated against 7,12-dimethylbenz(a)anthracene (DMBA)/croton oil-induced two-stage mouse skin carcinogenesis model. The compound was administered orally in carcinogen-induced mice in two different non-toxic doses: 2 mg/kg body weight and 3 mg/kg body weight. Significant inhibition in the incidence of papilloma formation (58–80%) as well as in the cumulative number of papilloma per papilloma-bearing mouse were observed in the treated groups as compared with the carcinogen control group. The compound was also found to significantly upregulate different phase II detoxifying enzymes in liver cytosol such as glutathione-S-transferase (P<0.01), catalase (P<0.01) and superoxide dismutase (SOD) (P<0.01) when measured after 15 days and also after 12 weeks of first DMBA treatment. Lipid peroxidation measured as the thiobarbituric acid reactive substances in liver microsomes was significantly inhibited (P<0.05) in a dose-dependent manner by diphenylmethyl selenocyanate. Thus the compound exerts its chemopreventive activity by reducing papilloma formation during chemically induced carcinogenesis, which in turn, may be through modulating the level of lipid peroxidation and phase II detoxifying enzyme system at the doses evaluated.

Administration of garlic and tomato can protect from carcinogen induced clastogenicity

Abstract Consumption of garlic and tomato has been associated with reduced risk of many human cancers. The effects of these two dietary items were studied experimentally on carcinogen [lsqb]DMBA[rsqb] induced clastogenicity in Swiss mice. Chromosomal aberrations, which are predictor of cancer risk, were found to be reduced in bone marrow cells of Swiss mice exposed to carcinogens. Significant reduction of chromosomal aberration was noted in bone marrow on day 21 and 30 (p

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, diphenylmethylseleno-cyanate, was tested on azoxymethane (15 mg/kg body wt) induced colon carcino genesis 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.

Influence of alpha-tocopherol during carcinogenesis in uterine cervix of mice.

The effect of supplemental alpha tocopherol and its mode of action were evaluated during carcinogenesis in uterine cervix of mice by chronic exposure to 20-methylcholanthrene (MC). Oral administration of alpha tocopherol restricted the progression of dysplastic changes in cervix uteri which lead to carcinoma in situ during chronic exposure to MC. Enhanced mitogenic stimulation of peripheral blood lymphocytes (PBL) indicating improved immune response was also noted following treatment. A decrease in micronucleus frequency in the vaginal exfoliated cells suggested reduced genotoxic effect of the carcinogen after alpha tocopherol administration. A decrease in lipid peroxides following ingestion of alpha tocopherol imply its protective role on DNA damage by oxidative free radicals. Similarly, elevated glutathione level and increased activities of glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase indicated involvement of alpha tocopherol in hosts detoxification system.

Wastewater Aquaculture by the Mudialy Fisherman's Cooperative Society in Kolkata, West Bengal: An Example of Sustainable Development

At the heart of one of the most densely populated mega-cities of India lies an eco-friendly and sustainable developmental business model. The city in question is Kolkata and the profitable but environmentally friendly venture that will be highlighted in this paper is that of wastewater-fed aquaculture practiced by a cooperative run by the local fishermen, namely Mudialy Fishermans Cooperative Society (MFCS). Initially the marshy wetlands of Mudialy used to be flooded with polluted waste water from the city and the local industrial complex. Ultimately, the polluted water was released to the sacred River Ganges. This cooperative society has radically transformed these wetlands into an urban fishery and a water-front recreational ecosystem. The present paper focuses on the incredible task completed by the MFCS and also reports the results of water-quality analyses to ascertain that conditions in the water bodies of MFCS are ideal for a profitable aquaculture practice. All the water quality parameters studied (physicochemical water parameters, concentration of different heavy metals, and zooplankton community structure) were well within the normal limits from the point of view of pisciculture. This proves the efficiency of the wastewater purification system adopted by the cooperative society. The major advantage of wastewater-fed aquaculture over conventional wastewater treatment is the large diversity of marketable products and therefore broad possibilities of income generation. Thanks to the poor fishermen of MFCS, the water drained from these wetlands into the River Ganges is no longer polluted.

Modulation of Cervical Carcinogenesis by Tamoxifen in a Mouse Model System

Insertion of cotton thread impregnated with beeswax and 20-methylcholanthrene (carcinogen) inside the canal of the uterine cervix in intact and oophorectomized mice results in the expression of dysplasia and carcinoma of the cervical epithelium. Based upon the experimental cervical carcinogenesis observed in this mouse model system, the present study shows distinctly the modulatory effect of tamoxifen on the incidence of cervical carcinoma. Besides this, tamoxifen significantly lengthens the latent period for both dysplasia and carcinoma in the cervical epithelium. This manifestation was found more marked in oophorectomized animals.

Abstract 2880: Spices suppress oxidative stress during DMBA induced skin carcinogenesis in mice, mimicking human non-melanoma skin cancer

Background: Cancer chemoprevention is the use of natural, synthetic or biologic substances to reverse, suppress, or prevent the development of cancer. Spices like cinnamon, cardamom and cumin are the naturally occurring phytoproducts that display an active cancer preventive strategy to inhibit, delay or reverse the human carcinogenesis. Aims and Objectives: Our aim of this study is to decipher the chemopreventive effect of aqueous infusion of the spices as a diet on DMBA induced skin carcinogenesis, which mimics UV radiation mediated non melanoma skin cancer that has high mortality rate if not diagnosed early. Research Design and Methodology: Female Swiss Albino Mice have been divided into 5 groups in each case. Normal control (NC) and DMBA treated control (CC) mice received acetone and DMBA/croton oil on it9s dorsally shaven skin for eight weeks, respectively. Aqueous suspensions of the spices were orally administered to three groups of mice either before or after or both before and after DMBA applications on the shaved skin during the entire study period. Treated skins were excised after harvesting the mice and H & E staining, immunohistochemistry assays for lipid peroxides, antioxidation enzymes activities, immunoblotting, cell proliferation and apoptosis were performed. Results: All the spices demonstrate inhibition of the skin papillomagenesis. The best chemopreventive actions of these spices were observed when the spice treatments were performed both before and after the induction of skin carcinogenesis by DMBA. An up-regulation of the phase II detoxification enzymes and induction of non-protein thiol antioxidants were observed in mice treated with the spices. Additionally, cumin and cardamom demonstrate downregulation of COX-2 expression, inhibit cell proliferation and block p53-induced apoptosis. Cardamom stimulates NRF2 and inhibits NF-κB transcription factors to demonstrate its beneficial action against skin carcinogenesis. Conclusion: Spices inhibit DMBA induced skin carcinoma in mice when treated early and it is believed to be due, at least in part, to the induction of cellular defense systems. We are in a process of identifying unique chemical components of these spices to maximize the benefits. References: 1. Das, I., and Saha, T.; Nutrition. (2009); 25(4):459-471. 2. Das, I., Das, S. and Saha, T.; Acta Histochem. (2009); (In Press) 3. Das, I., Rana, T., Sengupta, A., and Saha, T.; J. Biol. Chem. 2009; (In Revision) 4. Acharya, A, Das, I., Chandhok, D., and Saha, T.; Oxidative Stress and Cellular Longevity; 2009; (In Press) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2880.