cancer-prevention

Author: Rajesh Manian and Nagarajan Anusuya and Perumal Siddhuraju and Sellamuthu Manian

The stem bark and fruits of Ficus bengalensis L. and Ficus racemosa L. are used in India for the treatment of diabetes and a number of other diseases. Since these effects may be correlated with the presence of antioxidant compounds, methanol and 70% acetone (acetone:water, 70:30) extracts of F. bengalensis(aerial root) and F. racemosa (stem bark) were evaluated for their antioxidant activity and radical scavenging capacity in comparison with Camellia sinensis (L.) O. Kuntz (green tea). Methanol extracts of green tea and F. bengalensis and 70% acetone extract of F. racemosa contained relatively higher levels of total phenolics than the other extracts. The antioxidant potential of the extracts were assessed by employing different in vitro assays such as reducing power assay, DPPH, ABTS+ and OH radical scavenging capacities, peroxidation inhibiting activity through linoleic acid emulsion system, antihemolytic assay by hydrogen peroxide induced method and metal ion chelating ability. Though all the extracts exhibited dose dependent reducing power activity, methanol extracts of all the samples were found to have more hydrogen donating ability. Similar line of dose dependent activity has been maintained in all the samples in DPPH and OH scavenging systems. All the extracts exhibited antioxidant activity against the linoleic acid emulsion system (34–38%). The potential of multiple antioxidant activity was evident as it possessed antihemolytic activity and metal ion chelating potency.

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Author: Takeshi Ishii and Taiki Mori and Tomoko Tanaka and Daisuke Mizuno and Ryoichi Yamaji and Shigenori Kumazawa and Tsutomu Nakayama and Mitsugu Akagawa

Green tea polyphenol (–)-epigallocatechin-3-gallate (EGCG) has various beneficial properties including chemopreventive, anticarcinogenic, and antioxidant actions. The interaction with proteins known as EGCG-binding targets may be related to the anticancer effects. However, the binding mechanisms for this activity remain poorly understood. Using mass spectrometry and chemical detection methods, we found that EGCG forms covalent adducts with cysteinyl thiol residues in proteins through autoxidation. To investigate the functional modulation caused by binding of EGCG, we examined the interaction between EGCG and a thiol enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Concentration-dependent covalent binding of EGCG to GAPDH was found to be coupled to the irreversible inhibition of GAPDH activity. Mutation experiments revealed that EGCG is primarily bound to the cysteinyl thiol group of the active center, indicating that the irreversible inhibition of GAPDH is due to the covalent attachment of EGCG to the active-center cysteine. Moreover, using EGCG-treated cancer cells, we identified GAPDH as a target of EGCG covalent binding through specific interactions between catechols and aminophenyl boronate agarose resin. Based on these findings, we propose that the covalent modification of proteins by EGCG may be a novel pathway related to the biological activity of EGCG.

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Author: M. Pilar Almajano and Rosa Carbó and J. Angel López Jiménez and Michael H. Gordon

Tea polyphenols, especially the catechins, are potent antimicrobial and antioxidant agents, with positive effects on human health. White tea is one of the less studied teas but the flavour is more accepted than that of green tea in Europe. The concentrations of various catechins in 13 different kinds of infusion were determined by capillary electrophoresis. The total polyphenol content (Folin–Ciocalteu method), the trolox equivalent antioxidant capacity (TEAC value determined with the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation) and the inhibitory effects of infusions on the growth of some microorganisms were determined. Five different infusions (black, white, green and red teas and rooibos infusion) were added to a model food system, comprising a sunflower oil-in-water emulsion containing 0% or 0.2% bovine serum albumin (BSA), and the oxidative stability was studied during storage at 37 °C. Oxidation of the oil was monitored by determination of the peroxide value. The highest radical-scavenging activity observed was for the green and white teas. Emulsions containing these extracts from these teas were much more stable during storage when BSA was present than when it was not present, even though BSA itself did not provide an antioxidant effect (at 0.2% concentration). Rooibos infusion did not show the same synergy with BSA. Green tea and white tea showed similar inhibitions of several microorganisms and the magnitude of this was comparable to that of the commercial infusion 2 (C.I.2), “té de la belleza”. This tea also had an antioxidant activity comparable to green tea.

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Author: Giangiacomo Beretta and Sandra Furlanetto and Luca Regazzoni and Marina Zarrella and Roberto Maffei Facino

The aim of this work was to investigate in vitro the quenching activity of green tea polyphenols against α,β-unsaturated aldehyde, using 4-hydroxy-nonenal (HNE) as prototype and HPLC–ESI–MS/MS techniques. HNE is the most abundant and genotoxic product of oxidation of dietary polyunsaturated fatty acids, and is believed to be involved in the early stage of colorectal carcinogenesis on account of its genotoxic potential. Both epigallocatechin gallate (EGCG, 1.0–3.5 mM), the main constituent of green tea polyphenols, and a green tea aqueous extract are able to quench HNE (50 μM) in colorectal physiomimetic conditions (10 mM phosphate buffer, pH 8.0, 37 °C), giving rise to the formation of six diastereomeric covalent adducts at the ring A of EGCG, as indicated by their ESI–MS/MS fragmentation pathways. The specificity of the adduction positions was explained by 1H NMR experiments. HNE quenching is pH-dependent and maximum at pH 8.0. ESI–MS analysis showed no formation of 4-hydroxy-2,3-epoxy-nonanal, or adduction of the epoxide to EGCG. This implies that too little hydrogen peroxide (1 mM, 24 h incubation, FOX-2 method) develops from auto-oxidation of EGCG in our aerobic experimental conditions to oxidize HNE to its corresponding epoxide, so this mechanism is not responsible for the compound's disappearance. EGCG and green tea extract also quenched acrolein, another genotoxic α,β-unsaturated aldehyde, giving one predominant adduct and minor isobaric species, probably due the adduction of acrolein at different positions of the EGCG ring A. These results suggest that EGCG and green tea extract, beside the proposed mechanisms of chemoprevention that target multiple cell-signaling pathways that control cell proliferation and apoptosis in cancer cells, can also prevent protein carbonylation in the tumor tissue environment, depending on the pH of the medium surrounding the tissue, the type of tumor, the stage of dysregulation of lipid peroxidation and, finally, the stage of carcinoma development.

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Author: Rabia Alghazeer and Suhur Saeed and Nazlin K. Howell

Author: Márcia Bertipaglia de Santana and Marcos Gontijo Mandarino and Jefferson Rosa Cardoso and Isaías Dichi and Jane Bandeira Dichi and Alissana Ester Iakmiu Camargo and Bruno Alberto Fabris and Ricardo José Rodrigues and Elis Carolina Souza Fatel and Suzana Lucy Nixdorf and Andréa Name Colado Simão and Rubens Cecchini and Décio Sabbatini Barbosa

Author: Hye-Kyung Na and Young-Joon Surh

Frequent consumption of green tea, one of the most popular and widely consumed beverages, has been known to protect against development of various cancers according to numerous experimental and several population-based studies. Molecular mechanisms underlying chemopreventive effects exerted by green tea and its components have been extensively investigated. (−)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, has been shown to induce expression of glutathione S-transferase, glutathione peroxidase, glutamate cysteine ligase, hemeoxygenase-1, etc. that are involved in the elimination or inactivation of reactive oxygen species and electrophiles implicated in multi-stage carcinogenesis. The redox-sensitive transcription factor, nuclear factor erythroid 2 p45 (NF-E2)-related factor (Nrf2) plays a key role in regulating induction of phase II detoxifying or antioxidant enzymes. Thus, activation of Nrf2 is considered to be an important molecular target of many chemopreventive and chemoprotective agents. This review summarizes the molecular basis of chemoprevention and cytoprotection afforded by EGCG with emphasis on its ability to modulate Nrf2-mediated cellular events.

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Author: Jerzy Juśkiewicz and Zenon Zduńczyk and Adam Jurgoński and Łucja Brzuzan and Irena Godycka-Kłos and Ewa Żary-Sikorska

Rats with severe streptozotocin (STZ)-induced diabetes were subjected to dietary green tea extract supplementation at 2 doses (0.01% and 0.2%; GTL and GTH groups, respectively) to evaluate their effects on antioxidant, gastrointestinal, and renal parameters of experimental animals. The lower dietary supplementation reflects daily consumption of 3 cups of green tea for an average adult weighing 70 kg. Supplementation of a diet with green tea extract had no influence on elevated food intake, body weight loss, increased glucose concentration, or declined antioxidant capacity of water-soluble substances in plasma in the diabetic rats. In cases of intestinal maltase activity, attenuation of liver and kidney hypertrophy, triacylglycerol concentration, and aspartate aminotransferase activity in the serum, both dietary treatments normalized metabolic disorders caused by STZ injection to a similar extent. Unlike the GTL group, the GTH treatment significantly ameliorated development of diabetes-induced abnormal values for small intestinal saccharase and lactase activities, renal microalbuminuria, thiobarbituric acid-reactive substance content in kidney tissue, as well as total antioxidant status in the serum of rats. The GTH group was also characterized by higher antioxidant capacity of lipid-soluble substances in plasma and superoxide dismutase activity in the serum. Although the higher dose of green tea extract did not completely protect against STZ-induced hyperglycemia and oxidative stress in experimental rats, this study suggests that green tea extract ingested at high amounts may prove to be a useful therapeutic option in the reversal of diabetic dysfunction.

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Author: Paradee Auvichayapat and Montira Prapochanung and Oratai Tunkamnerdthai and Bung-orn Sripanidkulchai and Narong Auvichayapat and Bandit Thinkhamrop and Soontorn Kunhasura and Srisuda Wongpratoom and Supat Sinawat and Pranithi Hongprapas

This study was undertaken to investigate the effects of green tea on weight reduction in obese Thais. A randomized, controlled trial involving 60 obese subjects (body mass index, BMI > 25kg/m2) was conducted. All subjects consumed a Thai diet containing 3 meals (8373.6kJ/day) for 12weeks, prepared by the Nutritional Unit at Srinagarind Hospital. The diet contained 65% carbohydrates, 15% protein, and 20% fat. Body weight, BMI, body composition, resting energy expenditure, and substrate oxidation were measured at baseline, and during weeks 4, 8, and 12 of the study. Serum levels of leptin and urine VMA were measured at baseline and during the 12th week. Differences over time and between the treatments (green tea or placebo) over time were determined using two-factor ANOVA with repeated measures. In comparing the two groups, differences in weight loss were 2.70, 5.10, and 3.3kg during the 4th, 8th, and 12th weeks of the study, respectively. At the 8th and 12th weeks of the study, body weight loss was significantly different (P < 0.05). At the 8th week, the difference in resting energy expenditure was 183.38kJ/day (P < 0.001), the difference in the respiratory quotient was 0.02 (P < 0.05), and no significant differences existed in satiety score, food intake, or physical activity. Urine VMA was significantly different in the 12th week of the study (P < 0.05). We conclude that green tea can reduce body weight in obese Thai subjects by increasing energy expenditure and fat oxidation.

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Author: Maurizio Brausi and Federica Rizzi and Saverio Bettuzzi