Biofactors - Volume 13, issue 1-4

Authors: Makoto Shimizu, | Yoko Kobayashi, | Miho Suzuki, | Hideo Satsu, | Yusei Miyamoto,

Article Type: Research Article

Abstract: Intestinal glucose uptake is mainly performed by its specific transporters, such as SGLT 1, GLUT 2 and 5 expressed in the intestinal epithelial cells. By using human intestinal epithelial Caco-2 cells we observed that intestinal glucose uptake was markedly inhibited by tea extracts. While several substances in green tea seem to be involved in this inhibition, catechins play the major role and epicatechin gallate (ECg) showed the highest inhibitory activity. Since our Caco-2 cells did not …express enough amount of SGLT 1, the most abundant intestinal glucose transporter, the effect of ECg on SGLT 1 was evaluated by using brush border membrane vesicles obtained from the rabbit small intestine. ECg inhibited SGLT 1 in a competitive manner, although ECg itself was not transported via the glucose transporters. These results suggest that tea catechins could play a role in controlling the dietary glucose uptake at the intestinal tract and possibly contribute to blood glucose homeostasis. Show more

Keywords: glucose transporters, catechins, intestinal cells, absorption

Citation: BioFactors, vol. 13, no. 1-4, pp. 61-65, 2000

Authors: Masami Suganuma, | Eisaburo Sueoka, | Naoko Sueoka, | Sachiko Okabe, | Hirota Fujiki,

Article Type: Research Article

Abstract: Among various biochemical and biological activities of tea polyphenols, we believe inhibition of the expression and release of tumor necrosis factor-\alpha (TNF-\alpha ) is crucial, since our study with TNF-\alpha -deficient mice has revealed that TNF-\alpha is an essential factor in tumor promotion. We found that EGCG dose-dependently inhibited AP-1 and NF-\kappa B activation in BALB/3T3 cells treated with okadaic acid, resulting in inhibition of …TNF-\alpha gene expression. Furthermore, treatment with 0.1% gene expression as well as TNF-\alpha protein level in the lung of TNF-\alpha transgenic mice; and IL-1\beta and IL-10 gene expression in the lung was also inhibited by treatment with green tea extract, indicating that green tea inhibits both TNF-\alpha and the cytokines induced by TNF-\alpha in organs. We recently found synergistic effects of EGCG and cancer preventive agents such as tamoxifen and sulindac, on cancer preventive activity. Taken together, the results show that green tea is efficacious as a non-toxic cancer preventive for humans. Show more

Keywords: EGCG, sulindac, tamoxifen, tumor promotion

Citation: BioFactors, vol. 13, no. 1-4, pp. 67-72, 2000

Authors: Chung S. Yang, | Jee Y. Chung, | Guang-yu Yang, | Chuan Li, | Xiaofeng Meng, | Mao-Jung Lee,

Article Type: Research Article

Abstract: Tea {\it (Camellia sinensis)} preparations have been shown to inhibit tumorigenesis at the initiation, promotion, and progression stages in different animal models. The anti-proliferative effects of tea polyphenols may be a key mechanism, especially in the NNK-induced lung tumorigenesis model with mice. Studies with cell lines have demonstrated that tea polyphenols inhibit cell proliferation and induce apoptosis. The effective concentrations used in these studies (20--100 \mu M) are usually higher than those …observed in blood and tissues of humans and animals, which are in the low micromolar range. Glucuronide and sulfate conjugated and methylated catechins as well as ring fission products (due to intestinal microflora) have been observed in human plasma and urine. Purified green and black tea polyphenols inhibited the H-{\it ras} induced mitogen-activated protein kinases, AP-1 activities, and the growth of 30.7b Ras 12 and BES21 cells. Among the catechins, both the galloyl structure on the B ring and the gallate moiety are important for the inhibition. Both (- )-epigallocatechin-3-gallate and theaflavin-3,3' -digallate inhibited the phosphorylation of c-jun and p44/42 (ERK 1/2). More mechanistic and human studies in these areas will help us to understand the possible inhibitory action of tea against carcinogenesis in humans. Abbreviations: EGCG, (- )-epigallocatechin-3-gallate; EGC, (- )-epigallocatechin; ECG, (- )-epicatechin-3-gallate; EC, (- )-epicatechin; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; DGT, decaffeinated green tea; MAP kinase, mitogen activating protein kinase; AP-1, activator protein-1; NF\kappa B, nucleoprotein factor \kappa B. Show more

Citation: BioFactors, vol. 13, no. 1-4, pp. 73-79, 2000

Authors: Mamoru Isemura, | Kouichi Saeki, | Takashi Kimura, | Sumio Hayakawa, | Takeshi Minami, | Masaki Sazuka,

Article Type: Research Article

Abstract: Epigallocatechin gallate (EGCg) and theaflavins, a major constituent of green tea infusion and the constituents of black tea, respectively, were found to inhibit matrix metalloproteinases (MMPs) which are intimately associated with tumor invasion and metastasis. EGCg and related polyphenols exhibited apoptosis-inducing activity for several cancer cell lines including human stomach and colon cancer cells. Comparison of the activity of these compounds revealed the importance of the number and the steric disposition of …hydroxyl groups. A pyrogallol-type structure in a molecule is a minimum requirement for apoptosis induction of catechin compounds and that in the B ring has an important role in the activity. These data would provide useful information for designing anti-cancer agents on the basis of anti-inhibitory activity for MMPs and/or apoptosis-inducing activity. Show more

Keywords: epigallocatechin gallate, matrix metalloproteinase, apoptosis, tea polyphenol, anti-cancer agent

Citation: BioFactors, vol. 13, no. 1-4, pp. 81-85, 2000

Authors: Hoyoku Nishino, | Harukuni Tokuda, | Michiaki Murakoshi, | Yoshiko Satomi, | Mitsuharu Masuda, | Mari Onozuka, | Shino Yamaguchi, | Junko Takayasu, | Jun Tsuruta, | Masato Okuda, | Frederick Khachik, | Tomio Narisawa, | Nobuo Takasuka, | Masamichi Yano,

Article Type: Research Article

Abstract: Various natural carotenoids were proven to have anticarcinogenic activity. Epidemiological investigations have shown that cancer risk is inversely related to the consumption of green and yellow vegetables and fruits. Since \beta -carotene is present in abundance in these vegetables and fruits, it has been investigated extensively as possible cancer preventive agent. However, various carotenoids which co-exist with \beta -carotene in vegetables and fruits also have anti-carcinogenic activity. And some of …them, such as \alpha -carotene, showed higher potency than \beta -carotene to suppress experimental carcinogenesis. Thus, we have carried out more extensive studies on cancer preventive activities of natural carotenoids in foods; i.e., lutein, lycopene, zeaxanthin and \beta -cryptoxanthin. Analysis of the action mechanism of these natural carotenoids is now in progress, and some interesting results have already obtained; for example, \beta -cryptoxanthin was suggested to stimulate the expression of RB gene, an anti-oncogene, and p73 gene, which is known as one of the p53-related genes. Based on these results, multi-carotenoids (mixture of natural carotenoids) seems to be of interest to evaluate its usefulness for practice in human cancer prevention. Show more

Keywords: natural carotenoids, multi-carotenoids, cancer prevention

Citation: BioFactors, vol. 13, no. 1-4, pp. 89-94, 2000

Authors: Dae Joong Kim, | Nobuo Takasuka, | Hoyoku Nishino, | Hiroyuki Tsuda,

Article Type: Research Article

Abstract: An investigation was conducted to assess the chemopreventive potential of lycopene (LP), a naturally occurring hydrocarbon carotenoid found in tomatoes and their products, administered during the post-initiation stage in a multiorgan carcinogenesis model. One hundred eighteen B6C3F_1 mice of both sexes were subjected to combined treatment with diethylnitrosamine (DEN), N -methyl-N -nitrosourea (MNU) and 1,2-dimethylhydrazine (DMH) from day 11 after birth to week 9 (DMD treatment) …(groups 1 and 2) or given their vehicles (group 3). Then group 1 received LP (25 or 50 ppm in drinking water) for 21 weeks from weeks 11 to 32. Group 2 served as a carcinogen alone control and group 3 was given only LP (25 or 50 ppm). The incidences and multiplicities of lung adenomas plus carcinomas combined in male mice in group 1 receiving LP 50~ppm were significantly decreased as compared to the DMD alone or DMD and LP 25 ppm group values (75.0 vs 18.8%, While hepatocellular carcinomas were lacking in the DMD and LP groups, two cases were found in the DMD alone group (not statistically significant). The values for aberrant crypt foci (ACF) and tumors in the colon and kidney did not show any significant variation among the carcinogen-treated subgroups. The results of this study provide evidence that the tomato carotenoid, lycopene, may have potential as a chemopreventive agent against carcinogenesis in the male lung. Show more

Keywords: chemoprevention, lycopene (LP), mouse multiorgan carcinogenesis, lung cancer

Citation: BioFactors, vol. 13, no. 1-4, pp. 95-102, 2000

Authors: Teruo Kawada, | Yasutomi Kamei, | Atsushi Fujita, | Yoshifumi Hida, | Nobuyuki Takahashi, | Etsuro Sugimoto, | Tohru Fushiki,

Article Type: Research Article

Abstract: The adipocyte differentiation program is regulated by the sequential expression of transcriptional activators, mainly peroxisome proliferator activated receptor (PPAR) families. In the present study, we have decided to systematically examine the effects of vitamin A and its precursors, carotenoids and retinoids, on terminal differentiation from preadipocytes to adipocytes on the cellular and molecular aspects. The effects of active form of vitamin A, retinoic acid (RA), are believed to be mediated by specific nuclear receptor …proteins [retinoic acid receptor (RAR)] which are members of the steroid and thyroid/retinoid receptor superfamily of ligand dependent transcriptional regulators. RAR\alpha , RAR\gamma , RXR\alpha , and RXR\beta mRNA were abundant in adipose tissue and 3T3-L1 adipose cells. The autoregulated amplification of RAR\gamma mRNA was observed by these own ligands in 3T3-L1 cells. And, RA inhibited PPAR\gamma 2 expression more effectively and caused concomitantly a greater inhibition of adipocyte differentiation. These results suggest that the inhibitory action of adipocyte differentiation by carotenoids and retinoids are exhibited through the RAR up-regulation and the suppression of PPAR\gamma 2. The nature of the cross talk of vitamin A actions between the RARs, RXRs and PPARs via co-activator in adipose tissue will likely prove to be important for understanding the process of adipogenesis. Show more

Keywords: carotenoids, retinoids, vitamin A, nuclear receptor, adipocyte differentiation, fat soluble vitamin, peroxisome proliferator activated receptor

Citation: BioFactors, vol. 13, no. 1-4, pp. 103-109, 2000

Authors: Yoshifumi Tomita,

Article Type: Research Article

Citation: BioFactors, vol. 13, no. 1-4, pp. 111-112, 2000

Authors: Augustin Scalbert, | St\'ephanie D\'eprez, | Isabelle Mila, | Anne-Marie Albrecht, | Jean-Fran\c{c}ois Huneau, | Sylvie Rabot,

Article Type: Research Article

Abstract: Proanthocyanidins share common properties with other polyphenols, in particular their reducing capacity and ability to chelate metal ions. However, their polymeric nature clearly makes them different. They have a high affinity for proteins and their absorption through the gut barrier is likely limited to the molecules of low polymerization degree and to the metabolites formed by the colonic microflora, as suggested by {\it in vitro} experiments. The nutritional significance of proanthocyanidins is discussed in relation to …their physico-chemical properties and bioavailability. Show more

Keywords: proanthocyanidins, protein complexation, metal ion complexation, antioxidant capacity, bioavailability

Citation: BioFactors, vol. 13, no. 1-4, pp. 115-120, 2000

Authors: Takashi Yoshida, | Tsutomu Hatano, | Hideyuki Ito,

Article Type: Research Article

Abstract: Structure and function of polypehnols with high molecular weights (tannins) were briefly reviewed to better understand the significance of polyphenol-rich foods and beverages. In a survey of bioactive ellagiannins with a macrocyclic structure and/or a gluconic acid core, some new oligomeric ellagitannins (eucarpanins and elaeagnatins) have been found in species of Myrtaceae and Elaeagnaceae, and their structures were elucidated by spectroscopic and chemical methods. Cytotoxic activity against human oral tumor cell lines …and antibacterial activity against {\it Helicobacter pylori} have been evaluated for the ellagitannins obtained from both plants, and related compounds. The macrocyclic dimers, oentothein B, camelliin B and woodfordin C showed a remarkable cytotoxicity against human oral squamous cell carcinoma, but not against normal cells. These active tannins induced apoptosis of tumor cells. A potent antibacterial activity against {\it Helicobacter pylori} was exhibited by monomeric ellagitannins such as tellimagrandin I and stricitinin. Show more

Keywords: tannins, macrocyclic ellagitannin oligomers, ellagitannin with gluconic acid core, anti-{\it Helicobacter pylori} activity, cytotoxicity against human oral tumor cells

Citation: BioFactors, vol. 13, no. 1-4, pp. 121-125, 2000