Chemopreventive effects of green tea components on hepatic carcinogenesis.

Catechin components of green tea have been shown to possess anticarcinogenic properties possible related to their antioxidant activity. In the present study, a catechin containing green tea extract (GTE) was examined for its effect on three previously defined properties of liver tumor promoters, induction of cytolethality, inhibition of gap junctional intercellular communication, and induction of cell proliferation. Hepatocytes from male B6C3F1 mice were isolated and placed in primary culture. The effects of GTE of oxygen free radical-induced cytolethality was examined by coincubating GTE with the oxygen radical generating compounds paraquat, glucose oxidase (GO), and xanthine oxidase (XO). GTE prevented the induction of hepatocyte cytolethality by GO, XO, and paraquat in a dose-responsive manner. Similarly, GTE prevented the inhibition of gap junctional-mediated intercellular communication (measured by lucifer yellow dye coupling) by phenobarbital, lindane, and paraquat in a dose-dependent manner. The effect of GTE on hepatocyte DNA synthesis was examined in male mice containing preneoplastic liver lesions induced by diethylnitrosamine. GTE significantly decreased the labeling index in hepatic preneoplastic foci from animals treated with phenobarbital for 7 days. These studies suggest that the previous reported anticarcinogenic activity of green tea may be related to its effect on the tumor promotion stage of the cancer process.     

茶对口腔癌前病变的干预试验研究

将 5 9名经病理检查诊断为口腔粘膜白斑的患者 ,随机分为饮混合茶组 (2 9名 )和安慰剂组 (30名 )。混合茶组每天服用 3g混合茶 ,同时以 0 1g ml浓度的甘油溶液涂于患处 ;对照组给淀粉安慰剂和涂抹甘油 ,进行干预试验 6个月后 ,结果发现混合茶组有 37 9% (11 2 9)的患者白斑病损缩小 ,3 4% (1 2 9)的患者白斑病损增大 ,而安慰剂组仅 10 % (3 30 )的患者白斑病损缩小 ,6 7% (2 30 )的患者白斑病损增大。口腔脱落粘膜细胞微核发生率、每核银染核仁组织区 (AgNOR)数目和银染核仁组织区总面积 (TVNOR)及口腔粘膜组织细胞增殖抗原 (PCNA)增殖指数均降低 ,安慰剂组的变化不明显。结果显示混合茶可改善口腔粘膜白斑的病损 ,并预防口腔粘膜组织的DNA损伤和抑制其增殖 ,从而降低口腔癌前病变癌变的危险性 ,很可能对人类口腔癌有预防作用     

Chemopreventive effects of in vitro digested and fermented bread in human colon cells

Purpose

Bread as a staple food product represents an important source for dietary fibre consumption. Effects of wheat bread, wholemeal wheat bread and wholemeal rye bread on mechanisms which could have impact on chemoprevention were analysed in colon cells after in vitro fermentation.

Methods

Effects of fermented bread samples on gene expression, glutathione S-transferase activity and glutathione content, differentiation, growth and apoptosis were investigated using the human colon adenoma cell line LT97. Additionally, apoptosis was studied in normal and tumour colon tissue by determination of caspase activities.

Results

The expression of 76 genes (biotransformation, differentiation, apoptosis) was significantly upregulated (1.5-fold) in LT97 cells. The fermented bread samples were able to significantly increase glutathione S-transferase activity (1.8-fold) and glutathione content (1.4-fold) of the cells. Alkaline phosphatase activity as a marker of differentiation was also significantly enhanced (1.7-fold). The fermented bread samples significantly inhibited LT97 cell growth and increased the level of apoptotic cells (1.8-fold). Only marginal effects on apoptosis in tumour compared to normal tissue were observed.

Conclusions

This is the first study which presents chemopreventive effects of different breads after in vitro fermentation. In spite of differences in composition, the results were comparable between the bread types. Nevertheless, they indicate a potential involvement of this staple food product regarding the prevention of colon cancer.     

Genotoxic effects of green tea extract on human laryngeal carcinoma cells in vitro

Green tea (Camellia sinensis) contains several bioactive compounds which protect the cell and prevent tumour development. Phytochemicals in green tea extract (mostly flavonoids) scavenge free radicals, but also induce pro-oxidative reactions in the cell. In this study, we evaluated the potential cytotoxic and prooxidative effects of green tea extract and its two main flavonoid constituents epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) on human laryngeal carcinoma cell line (HEp2) and its cross-resistant cell line CK2. The aim was to see if the extract and its two flavonoids could increase the sensitivity of the cisplatin-resistant cell line CK2 in comparison to the parental cell line. The results show that EGCG and green tea extract increased the DNA damage in the CK2 cell line during short exposure. The cytotoxicity of EGCG and ECG increased with the time of incubation. Green tea extract induced lipid peroxidation in the CK2 cell line. The pro-oxidant effect of green tea was determined at concentrations higher than those found in traditionally prepared green tea infusions.     

Inhibitory effects of rosmarinic acid extracts on porcine pancreatic amylase in vitro

Porcine pancreatic alpha-amylase (PPA) was allowed to react with herbal extracts containing rosmarinic acid (RA) and purified RA. The derivatized enzyme-phytochemical mixtures obtained were characterized for residual amylase activity. These in vitro experiments showed that the amylase activity was inhibited in the presence of these phytochemicals. The extent of amylase inhibition correlated with increased concentration of RA. RA-containing oregano extracts yielded higher than expected amylase inhibition than similar amount of purified RA, suggesting that other phenolic compounds or phenolic synergies may contribute to additional amylase inhibitory activity. The significance of food-grade, plant-based amylase inhibitors for modulation of diabetes mellitus and other oxidation-linked diseases is hypothesized and discussed.     

Chemopreventive effects of dietary flaxseed on colon tumor development

Fatty acid composition of dietary fat plays a vital role in colon tumor development in animal models. Fats containing omega-6 fatty acids (e.g., corn oil) enhanced and omega-3 fatty acids (e.g., flaxseed oil) reduced chemically induced colon tumor development in rats. Lignans have also been shown to prevent colon tumor development in experimental animals. The objective of this investigation is to study the effects of dietary flaxseed meal, a source of both omega-3 fatty acid and lignans, on colon tumor development and compare them with the effects of dietary corn meal. Male Fischer rats, two groups of 24 each, were assigned to the AIN-93M diet supplemented with either 15% corn meal or 15% flaxseed meal, respectively. Carcinogenesis was initiated with subcutaneous injections of azoxymethane (15 mg/kg) once a week for 3 consecutive wk. After 35 wk of initiation, rats were anesthetized with ether. Blood was collected by cardiac puncture, and rats were sacrificed. The gastrointestinal tract was isolated. The site, size, and number of tumors were recorded. The fatty acid analysis of the collected serum and colon samples was performed. Expression of cyclooxygenase (COX)-1 and COX-2 was performed by Western blot method. Lignan levels in serum and colon samples were assayed. Colon tumor incidence, multiplicity, and size were found to be 82.6% and 29.4%; 1.3 and 0.3; and 44.4 and 5.3 mm(2) in corn and flaxseed meal groups, respectively. Colon and serum samples of the corn meal group showed higher levels of omega-6 fatty acid levels whereas the flaxseed meal group exhibited higher levels of omega-3 fatty acids. COX-1 and COX-2 expression in the flaxseed group was significantly lower (P < 0.05) as compared to the corn group. Dietary flaxseed meal containing high levels of omega-3 fatty acids and lignans is effective in preventing colon tumor development when compared with dietary corn meal possibly by increasing omega-3 fatty acid levels and decreasing COX-1 and COX-2 levels.     

Soy phytochemicals and tea bioactive components synergistically inhibit androgen-sensitive human prostate tumors in mice

Although high doses of single bioactive agents may have potent anticancer effects, the chemopreventive properties of the Asian diet may result from interactions among several components that potentiate the activities of any single constituent. In Asia, where intake of soy products and tea consumption are very high, aggressive prostate cancer is significantly less prevalent in Asian men. The objective of the present study was to identify possible synergistic effects between soy and tea components on prostate tumor progression in a mouse model of orthotopic androgen-sensitive human prostate cancer. Soy phytochemical concentrate (SPC), black tea and green tea were compared with respect to tumorigenicity rate, primary tumor growth, tumor proliferation index and microvessel density, serum androgen level and metastases to lymph nodes. SPC, black tea and green tea significantly reduced tumorigenicity. SPC and black tea also significantly reduced final tumor weights. Green tea did not reduce final tumor weight, although it tended to elevate (P = 0.14) the serum dihydrotestosterone (DHT) concentration. The combination of SPC and black tea synergistically inhibited prostate tumorigenicity, final tumor weight and metastases to lymph nodes in vivo. The combination of SPC and green tea synergistically inhibited final tumor weight and metastasis and significantly reduced serum concentrations of both testosterone and DHT in vivo. Inhibition of tumor progression was associated with reduced tumor cell proliferation and tumor angiogenesis. This study suggests that further research is warranted to study the role of soy and tea combination as effective nutritional regimens in prostate cancer prevention.     

Chemopreventive effects of dietary flaxseed oil on colon tumor development

Fatty acid composition of dietary fat, primarily the levels of omega-3 and omega-6 polyunsaturated fatty acids, has shown profound effect on colon tumor development in animal studies. Fats containing omega-6 fatty acids (for example, corn oil) enhanced and omega-3 fatty acids (for example, fish oil and mustard oil) reduced chemically induced colon tumors in rats. The purpose of this study was to investigate the effects of dietary flaxseed oil (containing alpha-linolenic acid, an omega-3 polyunsaturated fatty acid) on azoxymethane-induced colon tumor in rats and how it compared with the dietary corn oil-treated group. Male Fischer rats, separated into 2 groups of 30, were assigned to the AIN-93M diet, which was supplemented with either 15% corn oil or 15% flaxseed oil. Carcinogenesis was initiated with subcutaneous injections of azoxymethane (15 mg/kg) once a week for three consecutive weeks. Thirty-five weeks after initiation, the rats were sacrificed under ether anesthesia. Blood was collected by cardiac puncture. The gastrointestinal tract was isolated and flushed with ice-cold normal saline. The site, size, and number of tumors were recorded. The incidence and multiplicity of the tumors in the colon were determined. The fatty acid composition in the serum, colon, and tumors was estimated by using gas chromatography-flame ionization detection. Colon tumor incidence was found to be 100% and 54%, whereas multiplicity was found to be 3.1 and 0.7 tumors per rat in corn oil- and flaxseed oil-treated groups, respectively. Tumor size was significantly larger in the corn oil-treated group than in the flaxseed oil group. Colon and serum samples of the corn oil group showed an increase in the omega-6 fatty acid levels, whereas the flaxseed oil group exhibited an increase in the omega-3 fatty acid levels. The results indicate that dietary flaxseed oil, containing high levels of omega-3 fatty acids, is effective in preventing colon tumor development when compared with dietary corn oil containing omega-6 fatty acids in rats.     

In vivo and in vitro effects of beta-carotene and algae extracts in murine tumor models

Phycotene, an algae extract with known antineoplastic activity, was demonstrated to prolong, but not sustain, an increased survival rate in a murine fibrosarcoma model when it was combined with immunotherapy. It was further shown that splenocytes from phycotene and beta-carotene-treated survivors could not confer protection to a fresh tumor cell challenge in virgin mice after adoptive transfer. In a series of cytotoxicity assays, phycotene combined with immunization was demonstrated to enhance cell-mediated and complement-dependent cytotoxicity in the first 14-21 days. However, after 21 days, the phycotene and immunization groups exhibited a decreased ability to mediate immune cytotoxicity compared with immunization-only controls. This may serve to explain the in vivo findings that while survival was increased early on in active immunization and phycotene-treated mice, it eventually dropped to the level of the active immunization controls.     

In vivo and in vitro effects of β‐carotene and algae extracts in murine tumor models

Abstract

Phycotene, an algae extract with known antineoplastic activity, was demonstrated to prolong, but not sustain, an increased survival rate in a murine fibrosarcoma model when it was combined with immunotherapy. It was further shown that splenocytes from phycotene and β‐carotene‐treated survivors could not confer protection to a fresh tumor cell challenge in virgin mice after adoptive transfer. In a series of cytotoxicity assays, phycotene combined with immunization was demonstrated to enhance cell‐mediated and complement‐dependent cytotoxicity in the first 14–21 days. However, after 21 days, the phycotene and immunization groups exhibited a decreased ability to mediate immune cytotoxicity compared with immunization‐only controls. This may serve to explain the in vivo findings that while survival was increased early on in active immunization and phycotene‐treated mice, it eventually dropped to the level of the active immunization controls.     

茶和姜黄素对二甲基苯并蒽诱发地鼠口腔癌的预防作用

以 0 5 %二甲基苯并蒽 (DMBA) ,涂于地鼠左侧颊囊共 6周 (每周 3次 )。在最后一次涂DMBA后 ,分别给地鼠饮 0 6 %的绿茶粉水 ,涂抹姜黄素 1 0 μmol于左侧颊囊 (每周 3次 )或二者联合处理 1 8周。茶与姜黄素二者联合处理显著降低了口腔肿瘤发病率和癌发病率 ,肉眼肿瘤数目和体积、鳞癌和异常增生及乳头状瘤数目也分别显著降低。绿茶和姜黄素单独处理也分别降低了肿瘤数目、肿瘤体积和鳞癌数目。此外 ,绿茶还降低了异常增生数目和姜黄素降低了鳞癌发病率。茶与姜黄素单独或联合处理均抑制了单纯增生、异常增生和乳头状瘤病损的BrdU增殖指数 ,茶单独或与姜黄素联合增加了异常增生和鳞癌病损的凋亡指数 ,姜黄素单独或与茶联合抑制了乳头状瘤和鳞癌病损的新生血管形成。结果表明 ,茶与姜黄素对DMBA诱发的地鼠口腔癌在启动后阶段均有预防作用 ,其机制与抑制细胞增殖、诱导细胞凋亡和抑制细胞新生血管形成有关     

Chemopreventive effects of pomegranate seed oil on skin tumor development in CD1 mice

Pomegranate seed oil was investigated for possible skin cancer chemopreventive efficacy in mice. In the main experiment, two groups consisting each of 30, 4-5-week-old, female CD(1) mice were used. Both groups had skin cancer initiated with an initial topical exposure of 7,12-dimethylbenzanthracene and with biweekly promotion using 12-O-tetradecanoylphorbol 13-acetate (TPA). The experimental group was pretreated with 5% pomegranate seed oil prior to each TPA application. Tumor incidence, the number of mice containing at least one tumor, was 100% and 93%, and multiplicity, the average number of tumors per mouse, was 20.8 and 16.3 per mouse after 20 weeks of promotion in the control and pomegranate seed oil-treated groups, respectively (P <.05). In a second experiment, two groups each consisting of three CD(1) mice were used to assess the effect of pomegranate seed oil on TPA-stimulated ornithine decarboxylase (ODC) activity, an important event in skin cancer promotion. Each group received a single topical application of TPA, with the experimental group receiving a topical treatment 1 h prior with 5% pomegranate seed oil. The mice were killed 5 h later, and ODC activity was assessed by radiometric method. The experimental group showed a 17% reduction in ODC activity. Pomegranate seed oil (5%) significantly decreased (P <.05) tumor incidence, multiplicity, and TPA-induced ODC activity. Overall, the results highlight the potential of pomegranate seed oil as a safe and effective chemopreventive agent against skin cancer.     

Growth-inhibitory effects of vitamin E succinate on retrovirus-transformed tumor cells in vitro

Vitamin E succinate inhibited proliferation of C4#1 cells, an established avian retrovirus [reticuloendotheliosis virus (REV)]-transformed immature lymphoid tumor cell line, in a dose-dependent manner. The cytostatic effects of vitamin E succinate were reversible in that treated cells regained their ability to divide after vitamin E succinate removal. Possible mechanism(s) for the antiproliferative actions of vitamin E succinate were investigated. Analyses of C4#1 cell surface membrane antigen profiles and morphology indicated that vitamin E succinate was not inducing differentiation of the tumor cells to a more mature, differentiated, nonproliferative state. Five antioxidants, including a synthetic analogue of vitamin E, Trolox, as well as the active vitamin form, DL-alpha-tocopherol, were incapable of inhibiting C4#1 tumor cell growth, indicating that a mechanism of action other than or in addition to functions as an antioxidant may be operating. Cell cycle analyses suggested that C4#1 tumor cells treated with vitamin E succinate were blocked in the G0G1/early S phases of the cell cycle. Tumor growth arrested by vitamin E succinate did not affect the expression of the REV-encoded oncogene, v-rel, at either the RNA or protein level. These studies demonstrated that vitamin E, in the form of vitamin E succinate, inhibited the growth of retrovirus-transformed tumor cells in vitro and suggested that the antiproliferative effects of vitamin E succinate did not involve antioxidant properties but rather, as yet, unidentified mechanisms leading to cell cycle blockage.     

Evaluation of the in vitro antimutagenic effect of Doash tea aqueous extracts

Human carcinogens are formed mainly due to the lifestyle and diet that is followed. It is well known that dietary factors play a crucial role in the aetiology of human cancer. The new attractions of drug discovery using natural products remain an important issue in the current herbal medicine research. The present study aimed to evaluate the antimutagenic activity of the water extracts of Doash leaves against several known mutagens, both direct- and indirect-acting, belonging to different chemical classes. These classes are heterocyclic amines (HAs), polycyclic aromatic hydrocarbons and nitrosamines. The antimutagenic activity will be determined in Salmonella/microsomal system (Ames) using strains of Salmonella Typhimurium. Four Salmonella bacterial strains (TA98, TA97, TA100 and TA1530) were used in the present study. Results obtained showed that Doash extract possesses powerful antimutagenic properties, which impair the deleterious effects of various chemicals used in this study. One possible mechanism involved in this protection is the inhibition of the metabolic activation of chemical carcinogens to their reactive metabolites. We also suggest that the health benefits of Doash could be derived from the additive and synergistic combinations of the various phytochemicals present in Doash leaves. Other studies should also be conducted to determine the active components of Doash leaves, including macronutrients, micronutrients and other phytochemicals. Clinical studies should be performed before any claims that Doash consumption offers chemoprotection against cancer can be made.     

Lycopene inhibits the growth of normal human prostate epithelial cells in vitro

Lycopene has repeatedly been shown to inhibit the growth of human prostate cells in vitro. However, previous studies with lycopene have focused on cancer specimens, and it is still unclear whether this carotenoid affects the growth of normal human prostate cells as well. Therefore, we investigated the effects of lycopene on normal human prostate epithelial cells (PrEC) by treating them with synthetic all-E-lycopene (up to 5 micromol/L) and assessing proliferation via [3H]thymidine incorporation. The effects of lycopene on cell cycle progression were investigated via flow cytometry. To elucidate whether lycopene modulates cyclins involved in cell cycle progression, protein expressions of cyclins D1 and E were analyzed. The results show that lycopene significantly inhibited the growth of PrEC in a dose-dependent fashion. Flow cytometry revealed a significant cell cycle arrest in the G0/G1 phase. This effect was confirmed by inhibition of cyclin D1 protein expression, whereas cyclin E levels remained unchanged. The results demonstrate that lycopene inhibits growth of nonneoplastic PrEC in vitro. We hypothesize that lycopene might likewise inhibit the growth of prostatic epithelial cells in vivo. This might have an effect on prostate development and/or on enlargement of prostate tissue as found in benign prostate hyperplasia, a potential precursor of prostate cancer.     

Inhibitory effect of antioxidant extracts from various potatoes on the proliferation of human colon and liver cancer cells

Antioxidant extracts from 5 potato lines were evaluated for antioxidant activity, total phenolics, chlorogenic acid, anthocyanin content, and in vitro anticancer capacity. Analysis showed that Mexican wild species S. pinnatisectum had the highest antioxidant activity, total phenolic, and chlorogenic acid content. The proliferation of colon cancer and liver cancer cells was significantly inhibited by potato antioxidant extracts. The highest antiproliferative activity was observed in extracts of S. pinnatisectum and the lowest in Northstar. An inverse correlation was found between total phenolics and the EC(50) of colon cancer cell (R(2) = 0.9303), as well as liver cancer cell proliferation (R(2) = 0.8992). The relationship between antioxidant activity and EC(50) of colon cancer/liver cancer cell proliferation was significant (R(2) = 0.8144; R(2) = 0.956, respectively). A significant difference in inhibition of cancer cells (P < 0.01) existed between the 3 polyphenols: chlorogenic acid, pelargonidin chloride, and malvidin chloride, suggesting that chlorogenic acid was a critical factor in the antiproliferation of colon cancer and liver cancer cells.