title: Cytotoxicity of trans-chalcone and licochalcone A against breast cancer cells is due to apoptosis induction and cell cycle arrest.
abstract: Chalcones are precursors of flavonoids that exhibit structural heterogeneity and potential antitumor activity. The objective of this study was to characterize the cytotoxicity of trans-chalcone and licochalcone A (LicoA1) against a breast cancer cell line (MCF-7) and normal murine fibroblasts (3T3). Also the mechanisms of the anti-cancer activity of these two compounds were studied. The alkaline comet assay revealed dose-dependent genotoxicity, which was more responsive against the tumor cell line, compared to the 3T3 mouse fibroblast cell line. Flow cytometry showed that the two chalcones caused the cell cycle arrest in the G1 phase and induced apoptosis in MCF-7 cells. Using PCR Array, we found that trans-chalcone and LicoA trigger apoptosis mediated by the intrinsic pathway as demonstrated by the inhibition of Bcl-2 and induction of Bax. In western blot assay, the two chalcones reduced the expression of cell death-related proteins such as Bcl-2 and cyclin D1 and promoted the cleavage of PARP. However, only trans-chalcone induced the expression of the CIDEA gene and protein in these two experiments. Furthermore, transient transfections of MCF-7 using a construction of a promoter-luciferase vector showed that trans-chalcone induced the expression of the CIDEA promoter activity in 24 and 48h. In conclusion, the results showed that trans-chalcone promoted high induction of the CIDEA promoter gene and protein, which is related to DNA fragmentation during apoptosis.
authors.affiliation: Biotechnology Unit, Ribeirão Preto University, SP, Brazil.
authors.forename: Luis Felipe Buso
authors.initials: LF
authors.lastname: Bortolotto
authors.affiliation: Biotechnology Unit, Ribeirão Preto University, SP, Brazil.
authors.forename: Flávia Regina
authors.initials: FR
authors.lastname: Barbosa
authors.affiliation: Biotechnology Unit, Ribeirão Preto University, SP, Brazil; Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Silva
authors.affiliation: Biotechnology Unit, Ribeirão Preto University, SP, Brazil.
authors.forename: Tamires Aparecida
authors.initials: TA
authors.lastname: Bitencourt
authors.affiliation: Biotechnology Unit, Ribeirão Preto University, SP, Brazil.
authors.forename: Rene Oliveira
authors.initials: RO
authors.lastname: Beleboni
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Baek
authors.affiliation: Biotechnology Unit, Ribeirão Preto University, SP, Brazil.
authors.forename: Mozart
authors.initials: M
authors.lastname: Marins
authors.affiliation: Biotechnology Unit, Ribeirão Preto University, SP, Brazil. Electronic address: afachin@unaerp.br.
authors.forename: Ana Lúcia
authors.initials: AL
authors.lastname: Fachin
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002599:Chalcone / Q000008:administration & dosage / Q000494:pharmacology*; D047188:Chalcones / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase; D061986:MCF-7 Cells; D051379:Mice; D015394:Molecular Structure; D011401:Promoter Regions, Genetic
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047188:Chalcones; D002599:Chalcone; D007770:L-Lactate Dehydrogenase; C070840:licochalcone A
keywords: Apoptosis; CIDEA; Comet assay; Licochalcone A; MCF-7; PCR Array; Trans-chalcone