title: Curcumin exerts multiple suppressive effects on human breast carcinoma cells.
abstract: 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-beta estradiol. Curcumin inhibits the expression of ER downstream genes including pS2 and TGF-beta (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-beta estradiol. In addition, we demonstrate that curcumin exerts strong anti-invasive effects in vitro that are not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells. These anti-invasive 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.
authors.affiliation: Department of Breast Surgery, Cancer Hospital/Cancer Institute, Fudan University Medical Center, Shanghai, People's Republic of China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Shen
authors.forename: Can-Hui
authors.initials: CH
authors.lastname: Liu
authors.forename: Maryam R
authors.initials: MR
authors.lastname: Sartippour
authors.forename: Vay Liang
authors.initials: VL
authors.lastname: Go
authors.forename: David
authors.initials: D
authors.lastname: Heber
authors.forename: Mai
authors.initials: M
authors.lastname: Nguyen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D014158:Transcription, Genetic; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004965:Estrogen Antagonists; D011506:Proteins; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; C051838:TFF1 protein, human; D016211:Transforming Growth Factor alpha; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D003474:Curcumin