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.