Verma S P, Goldin B R, Lin P S
Department of Family Medicine and Community Health, Tufts University School of Medicine, Boston, MA 02111 USA.
Environ Health Perspect. 1998 Dec;106(12):807-12. doi: 10.1289/ehp.106-1533252.
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.
许多环境化学物质和农药已被发现具有雌激素活性，并已被证明能刺激雌激素受体阳性（ER阳性）的人类乳腺癌细胞生长。由于难以避免人类接触环境雌激素，一个潜在的重要研究领域是开发饮食策略，以防止环境雌激素刺激乳腺肿瘤生长。在此背景下，研究了姜黄素以及姜黄素与异黄酮的组合对农药o,p'-滴滴涕、环境污染物4-壬基酚和4-辛基酚诱导的ER阳性人类乳腺癌细胞（MCF-7和T47D）和ER阴性MDA-MB-231细胞的抑制作用。在48小时或6天的孵育时间测量时，姜黄素对T47D细胞的半数抑制浓度（IC50）为10微摩尔。姜黄素的IC50值在8-10微摩尔范围内，可抑制由10微摩尔浓度的4-壬基酚、4-辛基酚和o,p'-滴滴涕诱导的T47D细胞生长。10微摩尔的o,p'-滴滴涕、4-辛基酚或4-壬基酚诱导的MCF-7细胞中，姜黄素的IC50分别为9、39和>50微摩尔。姜黄素与异黄酮的组合能够抑制ER阳性细胞的诱导生长高达95%。对于MDA-MB-231细胞，姜黄素的IC50为17微摩尔，在存在25微摩尔染料木黄酮的情况下降至11微摩尔。姜黄素和染料木黄酮会使ER阳性和ER阴性细胞的形态发生剧烈变化。此处呈现的数据表明，姜黄素与异黄酮的混合物是对人类乳腺肿瘤细胞生长最有效的抑制剂。这些数据表明，天然植物化合物的组合可能对环境雌激素诱导的乳腺肿瘤生长具有预防和治疗作用。
