SCIENTIFIC ABSTRACTS
Seaweed is a popular dietary component in Japan and very rich source of essential elements. It is hypothesized that this dietary preference may be associated with the low incidence of benign and malignant breast disease in Japanese women. In animal and human studies, iodine administration has been shown to cause regression of both iodine-deficient goiter and benign pathological breast tissue. Iodine, in addition to its incorporation into thyroid hormones, is organified into anti-proliferative iodolipids in the thyroid; such compounds may also play a role in the proliferative control of extrathyroidal tissues. Selenium acts synergistically with iodine. All three mono-deiodinase enzymes are selenium-dependent and are involved in thyroid hormone regulation. In this way selenium status may affect both thyroid hormone homeostasis and iodine availability. Although there is suggestive evidence for a preventive role for iodine and selenium in breast cancer, rigorous prospective studies are needed to confirm this hypothesis. (Cann S, et al, Cancer Causes Control, 11(2): 121, 2000)
As it is impossible to use medicines for prevention of human breast cancer, in Japan, a lot of investigations using natural foods like as green tea, seaweed etc has been done. Seaweed was effective on breast cancer proliferation in rats. (Funahashi H, Nippon Rinsho, 58(6): 1267, 2000)

Edible brown seaweeds have antitumor activity and were effective from 70-84% in inhibiting colon cancer in rats, by boosting the animal�s immune systems, enabling it to better fight off the cancers. (Yanamoto I, Hydrobiologica, 116/117: 145, 1984)

Research on the properties and / or anticarcinogenic role of various types of seaweed, has led to the proposal that the mechanisms of seaweed's breast cancer preventing action were reduction of plasma cholesterol, binding of biliary steroids, the antioxygenic activity of the phospholipids, inhibition of carcinogenic fecal flora, binding of pollutants and the addition of important trace minerals to the diet. It is suggested that by eating seaweed, breast cancer may be prevented and that this dietary habit among the Japanese is an important factor in understanding their lower breast cancer rates. (Teas J, Med Hypotheses, 7(5): 601, 1981; Teas J, Nutrition Cancer 4(3): 217, 1983; Teas J, et al, Cancer Res 44(7): 2758, 1984)



Cancer

Selective antitumor activity in vitro from marine algae from Japan coasts. Harada H, Noro T, Kamei Y. Marine and Highland Bioscience Center, Saga University, Karatsu, Japan.
In vitro selective antitumor activity was tested as a general screening parameter for biologically active substances from a wide range of species of seaweed, 1446 samples of 306 species of marine algae from Japan's coasts. The algae extracts were prepared successively first by phosphate buffered saline (PBS) and then by methanol, and then tested for in vitro selective antitumor activity against murine lymphoid leukemia L1210 cells and for low cytotoxic activity against NIH-3T3 normal cells. Strong cytotoxic activity against L1210 cells was found in 47 species of algae, also showing similar cytotoxicity to mouse NIH-3T3 normal cells. However, four species of green algae showed strong activity specifically against L1210 cells, with low cytotoxicity to normal cells. Such selective activity was conspicuous in two brown and two green algae extracts. In particular, methanol extracts from the green alga, Cladophoropsis vaucheriaeformis, exhibited high viability (86%) to normal cells, showing selective cytotoxicity to tumor cells. This alga extract was no cytocidalic, but cytostatic against L1210 cells. Furthermore, the results of a cytotoxic spectrum test with 9 cell lines including those of L1210 and NIH-3T3 demonstrated that this extract acted strongly only against leukemic cell lines L1210 and P388.

Anticancer Res 1996 May-Jun;16(3A):1213-8
The dietary intake of Laminaria, a brown seaweed, and breast cancer prevention.
Teas J.
Based on epidemiological and biological data, Laminaria, a brown kelp seaweed, is proposed as an important factor contributing to the relatively low breast cancer rates reported in Japan. Several possible mechanisms for the influence of Laminaria on breast cancer are proposed: Laminaria is a source of nondigestible fiber, thereby increasing fecal bulk and decreasing bowel transit time; it changes the posthepatic metabolism of sterols; it contains an antibiotic substance that may influence fecal ecology; it contains 1-3 beta glucan, which alters enzymatic activity of fecal flora; and it stimulates the host-mediated immune response. It is suggested that Laminaria may play a role in preventing either the initiation of breast cancer or its promotion by endogenous physiological factors.
Publication Types:
Review
PMID: 6302638, UI: 83194310

Identification of heterogenous antimutagenic activities in the extract of edible brown seaweeds, Laminaria japonica (Makonbu) and Undaria pinnatifida (Wakame) by the umu gene expression system in Salmonella typhimurium (TA1535/pSK1002). Okai Y, Higashi-Okai K, Nakamura S
Division of Foods and Nutrition, Osaka Kun-ei Women's College, Japan.
A significant antimutagenic activity was found in the hot water-soluble extract from a common edible brown alga, Laminaria japonica (Makonbu in Japanese) which showed suppressive effects on umu gene expression of the SOS response against DNA damage in Salmonella typhimurium (TA1535/pSK1002). The extract showed a drastic antimutagenic activity against 2-acetylaminofluorene (2-AAF)- or 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1)-induced mutagenesis which requires liver-metabolizing enzymes, whereas the same extract exhibited weak but significant inhibitory effects on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)- or furylfuramide (AF-2)-induced mutagenesis in the absence of liver-metabolizing enzymes. Among these antimutagenic activities, the minor activity was found in the polysaccharide fraction of the extract which showed roughly equal antimutagenic activities against all the mutagens tested. The major activity was detected in the nonpolysaccharide fraction which exhibited a relatively strong antimutagenic activity against 2-AAF- or Trp-P-1-induced mutagenesis but a weak activity against MNNG- or AF-2-induced mutagenesis. The nonpolysaccharide fraction was further separated into high- or low-molecular-weight fractions and the latter fraction showed a much stronger activity than the former fraction. In addition, similar antimutagenic activities were detected in polysaccharide and nonpolysaccharide fractions from the extract of the other edible brown alga, Undaria pinnatifida (Wakame in Japanese). These experimental results indicate that the hot water-soluble extract of Laminaria japonica or Undaria pinnatifida contains heterogenous antimutagenic activities against typical genotoxic substances. The significance of this finding is discussed from the viewpoint of the protection against genotoxic substances by traditional edible seaweeds in Japan.
PMID: 7692279, UI: 94019480

Mutat Res 1984 Jul;127(2):113-8
Dietary seaweed (Laminaria) and mammary carcinogenesis in rats.
Teas J, Harbison ML, Gelman RS
To test the potential in vivo antitumor effect of dietary seaweed, we induced mammary tumors in female Sprague-Dawley rats with the carcinogen 7,12-dimethylbenz(a)anthracene. Twenty-one-day-old rats (n = 108) were divided into two groups. Controls were fed a standard semipurified diet, and experimental rats received the control diet with 5% Laminaria, a brown seaweed, replacing 5% alphacel . At 55 days of age, each rat received 5 mg 7,12-dimethylbenz(a)anthracene intragastrically. Rats were palpated for mammary tumors and weighed weekly for 26 weeks. Complete autopsies were then done on all rats. The seaweed diet did not alter weight gain or weights of body organs at autopsy. Experimental rats had a significant delay in the time to tumor (p = 0.007); median time until tumor was 19 weeks in experimental rats and 11 weeks in control animals. Among mammary adenocarcinoma tumor-bearing animals, experimental rats had fewer adenocarcinomas/individual (p less than 0.05). There was also an overall 13% reduction in the number of experimental rats with histologically confirmed adenocarcinomas (76% among the control rats compared to 63% among the experimental rats). Components of Laminaria which might account for the observed difference in mammary tumor growth are varied and include the sulfated polysaccharide fucoidan . Rats in the top row of cages had a significant (p = 0.01) delay in time to tumor compared to rats in the lower four rows. In each row, the seaweed-fed rats had a longer time to tumor than did the control rats.
PMID: 6426785, UI: 84205434


Cell Biol Toxicol 1997 Feb;13(2):95-102
Int J Dev Neurosci 1999 Aug-Oct;17(5-6):653-63
Cells encapsulated in alginate: a potential system for delivery of recombinant proteins to malignant brain tumours.
Read TA, Stensvaag V, Vindenes H, Ulvestad E, Bjerkvig R, Thorsen F
Department of Anatomy and Cell Biology, University of Bergen, Norway. t-a.read@pki.uib.no
[Medline record in process]
Growth and progression of malignant brain tumours occurs in a micromilieu consisting of both tumour and normal cells. Several proteins have been identified with the potential of interfering directly with tumour cells or with the neovascularisation process, thereby inhibiting tumour growth. A continuous delivery of such inhibitory proteins to the tumour microenvironment by genetically engineered cells could theoretically be of considerable therapeutic importance. In this study we have investigated the growth characteristics of cells encapsulated in alginate, which represents a potential delivery system for recombinant proteins that may have antitumour effects. Three different cell lines, NHI 3T3, 293 and BT4C were encapsulated in alginate, which is an immuno-isolating substance extracted from brown seaweed. The encapsulated cells were observed at specific intervals during a 4-month period after in vitro propagation and as transplants into the cortex of BD-IX rats. Morphological studies showed that encapsulated cells proliferated and formed spheroids within the alginate in the in vitro cultures and after implantation into the brain. Even after 4 months in vivo a substantial amount of living cells were observed within the alginate beads. A vigorous infiltration of mononuclear cells was observed in the brain bordering the alginate beads, one week after implantation. However, there was a gradual decrease of mononuclear cells at the border zone beyond the first week of implantation. The majority of inflammatory cells were reactive microglia and invading monocytes, as verified by immunohistochemistry. The data further shows that alginate encapsulated cells can be frozen in liquid N2 and will retain their viability and proliferative capacity.
PMID: 10571425, UI: 20036203


Oncology 1989;46(5):343-8
Anticancer potential of dietary seaweed extract, on Lewis lung carcinoma in comparison with chemical immunomodulators and on cyclosporine-accelerated AKR leukemia.
Furusawa E, Furusawa S
Department of Pharmacology, School of Medicine, University of Hawaii, Honolulu.
Viva-Natural, extracted from a dietary seaweed, containing a macrophage-activating polysaccharide, has been confirmed to be active against intraperitoneally implanted Lewis lung carcinoma (LLC) and spontaneous AKR T cell leukemia. The antitumor potential against LLC has been evaluated in comparison with standard synthetic immunomodulators such as pyran copolymer (MVE-2), isoprinosine, levamisole, and tilorone while manipulating the immune systems by immunosuppressive agents, cyclophosphamide (CY) and 2-chloroadenosine. The anti-LLC activity of Viva-Natural has been found to be superior to that of isoprinosine but inferior to that of MVE-2. LLC-enhancing effect of CY could be partially reserved by the subsequent administration of Viva-Natural or MVE-2 but not by isoprinosine. 2-Chloroadenosine, a specific macrophage inhibitor, abrogated the anti-LLC activity of Viva-Natural and isoprinosine but not the activity of MVE-2. Levamisole and tilorone showed no anti-LLC activity. Ethanol-precipitable fraction of water-soluble part of Viva-Natural (crude polysaccharide) demonstrated curative activity similar to that of MVE-2. Viva-Natural reversed the potentiation effect of ciclosporin on the development of leukemia in AKR mice at preleukemic stage.
PMID: 2476696, UI: 89385425


Cancer Lett 1986 Feb;30(2):125-31
The effect of dietary or intraperitoneally injected seaweed preparations on the growth of sarcoma-180 cells subcutaneously implanted into mice. Yamamoto I, Maruyama H, Takahashi M, Komiyama K
Sixteen preparations from 9 edible seaweeds including powdered weed (P), hot-water extract (E), the non-dialyzable fraction (I) of E and the residue (R) of hot-water extraction were incorporated into a basic diet, and they were given to mice implanted with Sarcoma-180 cells s.c., for 5 weeks. Consequently, diets with 6 preparations, E of Laminaria angustata, P and E of Laminaria angustata var. longissima, and P, E and R of Laminaria japonica var. ochotensis, were found to be effective, with inhibition ratios ranging from 70.3% to 83.6%. Intraperitoneal injection of 10 preparations from 6 edible seaweeds, including the above 3 weeds, were also noted to be effective in the same test system, with inhibition ratios ranging from 61.9% to 95.2%.
PMID: 3955535, UI: 86161437


Inhibitory effect of oversulfated fucoidan on invasion through reconstituted basement membrane by murine Lewis lung carcinoma.
Soeda S, Ishida S, Shimeno H, Nagamatsu A
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University.
We investigated the effects of native, oversulfated, and desulfated fucoidans and heparin on the invasion of 3 LL cells through Matrigel. Of the four polysaccharides tested, oversulfated fucoidan was the most potent inhibitor of tumor cell invasion and inhibited most potently and specifically the tumor cell adhesion to laminin. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of the binding of elastase-cleaved laminin to fucoidan- and heparin-Sepharoses showed that both polysaccharides bound to the 62 and 56 kDa fragments. Pretreatment of 3LL cells with native or oversulfated fucoidan reduced their adhesive potency to laminin. The two fucoidans inhibited further the laminin binding of 3 LL cells which had been pretreated with a laminin-based pentapeptide, YIGSR. These results suggest that fucoidan specifically binds to not only the heparin binding domain(s) of laminin but also site(s) other than the cell surface laminin receptor. 3 LL cells secreted a 50 kDa form of urokinase-type plasminogen activator (u-PA). The extracellular level of u-PA activity was increased 1.7 times by addition of laminin but not type IV collagen. Oversulfated fucoidan most potently reduced the increased u-PA levels. Therefore, the reduction in in vitro invasiveness of 3 LL cells in response to either fucoidan or its oversulfated derivative may result from an inhibition of physical interaction between the tumor cells and the Matrigel (laminin), followed by a suppression of the laminin-induced increase in extracellular u-PA.
PMID: 7829400, UI: 95130424