In our study, we present experimental evidence suggesting that curcumin exerts multiple different suppressive effects on human breast carcinoma cells in vitro. Our experiments demonstrate that curcumin's antiproliferative effects are estrogen dependent in ER (estrogen receptor)-positive MCF-7 cells, being more pronounced in estrogen-containing media and in the presence of exogenous 17-␤ estradiol. Curcumin inhibits the expression of ER downstream genes including pS2 and TGF-␤ (transforming growth factor) in ER-positive MCF-7 cells, and this inhibition is also dependent on the presence of estrogen. Curcumin also decreases ERE (estrogen responsive element)-CAT activities induced by 17-␤ estradiol. In addition, we demonstrate that curcumin exerts strong antiinvasive effects in vitro that are not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells. These antiinvasive effects appear to be mediated through the downregulation of MMP-2 (matrix metalloproteinase) and the upregulation of TIMP-1 (tissue inhibitor of metalloproteinase), 2 common effector molecules that have been implicated in regulating tumor cell invasion. Our study also demonstrates that curcumin inhibits the transcript levels of 2 major angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic fibroblast growth factor) mainly in ER-negative MDA-MB-231 cells. © 2002 Wiley-Liss, Inc. Key words: curcumin; chemoprevention; breast cancer; angiogenesis; estrogenBreast cancer chemoprevention is the subject of substantial research efforts to improve the health of women in the United States. Epidemiologic surveys suggest that diet has an impact on cancer incidence. Frequent consumption of vegetables and fruits decreases the risk for human cancer. 1,2 Although risk reduction by nutritional intervention alone may not be sufficient to protect high-risk individuals against cancer development, it would be very useful to identify agents with chemopreventive potency and to evaluate them in combination with nutritional intervention. 3,4 Recently, attention has been focused on identifying dietary phytochemicals that have the ability to inhibit the processes of carcinogenesis. Extracts of plants or their fractionated ingredients are found to possess inhibitory effects against chemically induced carcinogenesis. 5 Curcumin is a major component of turmeric, the dried rhizome of Curcuma longa L., which is commonly used as a yellow coloring and flavoring agent in food items in Asian countries. Commercial-grade curcumin has shown anticarcinogenic activity in animals as indicated by the ability to block colon tumor initiation induced by azoxymethans 6 and skin tumor promotion induced by phorbol ester. 7 Curcumin also has been reported to possess antiinflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipooxygenase/cyclooxygenase, 8,9 xanthine dehydroxygenase/oxidase 10 and nitric oxide synthase (NOS). 11,12 Recently, it has been shown that the administration of synthetic curcumin in the diet during t...

To study the BRCA1 mutations in eastern Chinese patients with early onset breast cancer and affected relatives, 41 patients' genomic DNA from peripheral mononuclear blood cells was studied by using single strand conformational polymorphism (SSCP) and DNA sequencing. The BRCA1 mutations were detected in the whole gene sequence. Three novel disease-causing mutations (c.582C>T, c.735C>T and c.2790delT) occurred in all the patients. Two occurred in the patients younger than 35 years old (9.1%) and one in the patients with affected relatives (5%). Additional sequence variants identified included a novel missense mutation of unknown significance and six polymorphisms. The prevalence of BRCA1 mutations in Chinese patients in Shanghai with early onset breast cancer is similar to that observed in western women, but the incidence of mutations in breast cancer patients in Shanghai with affected relatives isn't as high as that in western women.