title: Chalcone inhibits the proliferation of human breast cancer cell by blocking cell cycle progression and inducing apoptosis.
abstract: Chalcones are discussed to represent cancer preventive food components in a human diet that is rich in fruits and vegetables. In this study, we examined chalcone (1,3-diphenyl-2-propenone) for its effect on proliferation in human breast cancer cell lines, MCF-7 and MDA-MB-231. The results showed that chalcone inhibited the proliferation of MCF-7 and MDA-MB-231 by inducing apoptosis and blocking cell cycle progression in the G2/M phase. Immunoblot assay showed that chalcone significantly decreased the expression of cyclin B1, cyclin A and Cdc2 protein, as well as increased the expression of p21 and p27 in a p53-independent manner, contributing to cell cycle arrest. An enhancement in Fas/APO-1 and its two form ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), was responsible for the apoptotic effect induced by chalcone. In addition, chalcone also triggered the mitochondrial apoptotic signaling by increasing the amount of Bax and Bak and reducing the level of Bcl-2 and Bcl-X(L), and subsequently activated caspase-9 in MCF-7 and MDA-MB-231 cells. Taken together, our study suggests that the blockade of cell cycle progression and initiation of cell apoptotic system may participate in the antiproliferative activity of chalcone in human breast cancer cells.
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
authors.forename: Y L
authors.initials: YL
authors.lastname: Hsu
authors.forename: P L
authors.initials: PL
authors.lastname: Kuo
authors.forename: W S
authors.initials: WS
authors.lastname: Tzeng
authors.forename: C C
authors.initials: CC
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002599:Chalcone / Q000494:pharmacology*; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein; D016195:G2 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D008562:Membrane Glycoproteins / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D048069:Tumor Necrosis Factors / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D019925:Cyclin A; D019926:Cyclin B; D056744:Cyclin B1; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D048069:Tumor Necrosis Factors; D051020:bcl-X Protein; D002599:Chalcone; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases