Many environmental chemicals and pesticides have been found to be estrogenic and have been shown to stimulate the growth of estrogen receptor-positive (ER-positive) human breast cancer cells. Since it is difficult to avoid human exposure to environmental estrogens, a potentially important area of research is the development of dietary strategies to prevent the stimulated growth of breast tumors by environmental estrogens. In this context, the inhibitory action of curcumin and a combination of curcumin and isoflavonoids were studied in ER-positive human breast cancer cells (MCF-7 and T47D) and ER-negative MDA-MB-231 cells induced by the pesticide o,p'-DDT and the environmental pollutants 4-nonylphenol and 4-octylphenol. The median inhibitory concentration (IC50) for curcumin in T47D cells was 10 microM when measured at either a 48-hr or a 6-day incubation time. The IC50 value for curcumin was within the 8-10 microM range for inhibiting the growth of T47D cells induced by a 10- microM concentration each of 4-nonylphenol, 4-octylphenol, and o, p'-DDT. The IC50 for curcumin in MCF-7 cells induced by 10 microM of either o,p'-DDT, 4-octylphenol, or 4-nonylphenol were 9, 39, and >50 microM, respectively. A combination of curcumin and isoflavonoids was able to inhibit the induced growth of ER-positive cells up to 95%. For MDA-MB-231 cells, the IC50 for curcumin was 17 microM, which was reduced to 11 microM in the presence of 25 microM genistein. Curcumin and genistein induce drastic changes in the morphological shape of both ER-positive and ER-negative cells. Data presented here indicate that a mixture of curcumin and isoflavonoids is the most potent inhibitor against the growth of human breast tumor cells. These data suggest that combinations of natural plant compounds may have preventive and therapeutic applications against the growth of breast tumors induced by environmental estrogens.