Chalcone inhibits the proliferation of human breast cancer cell by blocking cell cycle progression and inducing apoptosis

• Published in: Food and chemical toxicology 2006-05, Vol.44 (5), p.704-713
• Main Authors: Hsu, Y.L., Kuo, P.L., Tzeng, W.S., Lin, C.C.
• Format: Article
• Language: English
• Subjects: anticarcinogenic activity; Antineoplastic Agents - pharmacology; antinutritional factors; antiproliferative activity; Apoptosis; Apoptosis - drug effects; bcl-X Protein - metabolism; Biological and medical sciences; Breast cancer; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Breast Neoplasms - prevention & control; Caspase 9; Caspases - metabolism; cell culture; Cell cycle; Cell Cycle - drug effects; cell cycle arrest; cell division; Cell Division - drug effects; cell lines; Chalcone; Chalcone - pharmacology; chemical composition; Cyclin A - metabolism; Cyclin B - metabolism; Cyclin B1; Dose-Response Relationship, Drug; Fas ligand; Fas Ligand Protein; Fas/APO-1; G2 Phase - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Gynecology. Andrology. Obstetrics; Humans; Immunoblotting; interphase; Mammary gland diseases; Medical sciences; Membrane Glycoproteins - metabolism; Mitosis - drug effects; plant-based foods; Proto-Oncogene Proteins c-bcl-2 - metabolism; Toxicology; Tumor Cells, Cultured; Tumor Necrosis Factors - metabolism; Tumors
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2005.10.003

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.