[Analysis of anti-proliferation of curcumin on human breast cancer cells and its mechanism].
OBJECTIVE
To study the suppressive effects of curcumin on breast carcinoma cells and the mechanism.


METHODS
Estrogen receptor (ER) positive human breast cancer line MCF-7 and ER negative human breast cancer line MDA-MB-231 were cultured 17-beta estradiol and curcumin were added into the culture. Northern blot hybridization and Western blots were performed to detect the expression of mRNA and protein. The human ERE promoter activity was analyzed by transient transfection with CAT-reporter constructs. Invasion experiments were conducted with a Matrigel invasion chamber.


RESULTS
Curcumin inhibit the proliferation in both estrogen receptor (ER) positive MCF-7 cells and ER negative MDA-MB-231 cells. Curcumin's antiproliferative effects are estrogen dependent in ER positive MCF-7 cells. Curcumin inhibits the expression of ER downstream genes including pS2 and TGF-alpha (transforming growth factor-alpha) in ER-positive MCF-7 cells, and this inhibition is also dependent on the presence of estrogen. In addition, curcumin exerts strong anti-invasive effects in vitro which was not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells. These anti-invasive effects appeared to be mediated through the down-regulation of MMP-2 (matrix metalloproteinase) and the up-regulation of TIMP-1 (tissue inhibitor of metalloproteinase). Curcumin inhibited the transcript levels of two major angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic fibroblast growth factor) in ER-negative MDA-MB-231 cells.


CONCLUSIONS
Curcumin exerts multiple suppressive effects on breast carcinoma cells;it's mechanism of chemoprevention is pleiotropic.
Di
Gen-hong
GH
Breast Surgery Department of Cancer Hospital, Fudan University, Shanghai 200032, China.
Li
He-cheng
HC
Shen
Zhen-zhou
ZZ
Shao
Zhi-min
ZM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D005260:Female; D006801:Humans; D011506:Proteins / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000235:genetics; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011506:Proteins; D011960:Receptors, Estrogen; C051838:TFF1 protein, human; D016211:Transforming Growth Factor alpha; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D003474:Curcumin