Seaweed as chemoprevention: From breast cancer epidemiology to breast cancer cell culture.

B172

Seaweeds are commonly eaten in Japan and Korea, where rates of hormonally sensitive cancers of the breast and prostate are significantly lower than in other developed nations. Japanese women who do develop breast cancer live longer. GI tract cancers are higher in these countries, leading to the hypothesis that dietary seaweed might enhance some cancers but inhibit others. However, epidemiological investigations in Japan have reported that for all GI tract cancers except rectal cancer, there is a significant protective association between increased consumption of seaweeds and lower risk. In the ongoing study of Japan Nurses' Health Study, breast cancer rates among women who consumed miso soup six or more times a week had half the risk of breast cancer compared to women who ate miso soup infrequently. As miso soup is a hot water extract of seaweed, miso, and vegetables, this finding adds support to the many in vitro and in vivo studies of seaweed-induced cancer inhibition. An average of 5-7 grams (dry weight) of seaweed are eaten daily in Japan, and this is even higher for nursing mothers. Although seemingly a small amount, when seaweeds are refreshed in water, they expand to about 10 times their dry weight volume, and hence become a significant part of the diet. METHODS: In this study, we compared water extracts of a range of common dietary seaweeds in three cell lines (estrogen sensitive MCF-7 breast cancer cells, estrogen insensitive MDA-MB-231 breast cancer cells, and hormone insensitive HCT-15 colon cancer cells). Cell proliferation was assessed by MTS, and inhibition of DNA synthesis was confirmed by BrdU assays. Further studies of cell cycle dynamics were done using flow cytometry. To visually study cell proliferation inhibition, we used DAPI confocal imaging. Apoptotic pathways were investigated using caspase 3/7 stimulation assays. RESULTS: Hormone insensitive cancer cells (HCT-15 and MDA-MB-231) showed the greatest cancer cell inhibition when exposed to seaweed extracts. DNA synthesis was inhibited, and for MDA-MB-231 cells, a clear cell cycle arrest in the G1 phase was seen. Confocal microscopy revealed patterns of DNA fragmentation. There was a range in the ability of different seaweeds to inhibit cell proliferation and only a few of the seaweeds significantly stimulated caspase 3/7. CONCLUSIONS: In seaweed research, specific unique components of brown seaweeds (fucoidan, fucoxanthin, alginic acid, laminarin) have each demonstrated cancer cell inhibition. However, we found that red seaweeds, which lack these components, also showed similar inhibition, suggesting that other water soluble chemicals derived from seaweeds my be important in understanding the anticarcinogenic properties of dietary seaweeds. Culinary seaweeds may help explain lower cancer rates observed among people in Japan.