title: Anti-carcinogenic effect of a new analogue 4'-chloroflavanone from flavanone in human breast cancer cells.
abstract: We investigated the antiproliferative effects of synthetic flavanone derivatives using an MTT assay in MCF-7 and MDA-MB-453 cells. When cells were treated with synthetic flavanone derivatives in concentrations ranging from 1 to 200 microM for 48 h, cell growth decreased at concentrations >50 microM. 4'-Chloroflavanone is more potent than flavanone among the synthetic flavanone derivatives. Exposure to 4'-chloroflavanone at 50 microM for 48 h caused cell cycle arrest in both MCF-7 and MDA-MB-453 cells. In addition, when 4'-chloroflavanone caused G1/S phase arrest, a decrease in CDK4 and cyclin D, together with an increase in p21Cip1, was observed in the cells. The p21Cip1 is a downstream target of p53 that may be affected by the activation of p53 by 4'-chloroflavanone. These results indicate that activation of p53 played some role in 4'-chloroflavanone-induced cell cycle arrest of human breast cancer cells. 4'-Chloroflavanone increased cytochrome c expression and decreased the expression of caspase-3, but did not change the expression of Bcl-2 and Bax. Activation of cytochrome c and its downstream target, caspase-3, is suggested to be an important inducer of the apoptosis process by 4'-chloroflavanone. 4'-Chloroflavanone inhibits cell proliferation through G1/S phase disruption and may induce apoptosis. Based on our findings, we propose that 4'-chloro-flavanone is useful as an anticancer drug.
authors.affiliation: Plant Resources Research Institute, Duksung Women's University, Tobong-ku, Seoul 132-714, Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Choi
authors.forename: Jae In
authors.initials: JI
authors.lastname: Lee
authors.forename: Gun-Hee
authors.initials: GH
authors.lastname: Kim
mesh_terms: D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016213:Cyclins / Q000378:metabolism; D005260:Female; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans
chemical_list: C548298:4'-chloroflavanone; D016588:Anticarcinogenic Agents; D016213:Cyclins; D044950:Flavanones; D005419:Flavonoids; C028610:flavanone