Antiproliferative activity of goniothalamin enantiomers involves DNA damage, cell cycle arrest and apoptosis induction in MCF-7 and HB4a cells

Autor: Lilian Areal Marques, Elaine Aparecida de Camargo, Gláucia Fernanda Rocha D'Epiro, Glenda Nicioli da Silva, Fernando César de Macedo Júnior, Simone Cristine Semprebon, Mário Sérgio Mantovani, Andressa Megumi Niwa
Přispěvatelé: Universidade Estadual de Londrina (UEL), Universidade Estadual Paulista (Unesp)
Rok vydání: 2015
Předmět:
Zdroj: Web of Science
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
ISSN: 1879-3177
Popis: Made available in DSpace on 2018-11-26T16:19:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-12-25 (R)-goniothalamin (R-GNT) is a styiyllactone that exhibits antiproliferative property against several tumor cell lines. (S)-goniothalamin (S-GNT) is the synthetic enantiomer of R-GNT, and their biological properties are poorly understood. The aim of this study was to evaluate the antiproliferative mechanisms of (R)-goniothalamin and (S)-goniothalamin in MCF-7 breast cancer cells and HB4a epithelial mammary cells. To determine the mechanisms of cell growth inhibition, we analyzed the ability of R-GNT and S-GNT to induce DNA damage, cell cycle arrest and apoptosis. Moreover, the gene expression of cell cycle components, including cyclin, CDKs and CKIs, as well as of genes involved in apoptosis and the DNA damage response were evaluated. The natural enantiomer R-GNT proved more effective in both cell lines than did the synthetic enantiomer S-GNT, inhibiting cell proliferation via cell cycle arrest and apoptosis induction, likely in response to DNA damage. The cell cycle inhibition caused by R-GNT was mediated through the upregulation of CIP/KIP cyclin-kinase inhibitors and through the downregulation of cyclins and CDKs. S-GNT, in turn, was able to cause GO/G1 cell cycle arrest and DNA damage in MCF-7 cells and apoptosis induction only in HB4a cells. Therefore, goniothalamin presents potent antiproliferative activity to breast cancer cells MCF-7. However, exposure to goniothalamin brings some undesirable effects to non-tumor cells HB4a, including genotoxicity and apoptosis induction. (C) 2015 Elsevier Ltd. All rights reserved. Univ Estadual Londrina, Dept Biol Geral, BR-86051990 Londrina, PR, Brazil Univ Estadual Paulista, Dept Patol, Botucatu, SP, Brazil Univ Estadual Londrina, Dept Quim, BR-86051990 Londrina, PR, Brazil Univ Estadual Paulista, Dept Patol, Botucatu, SP, Brazil
Databáze: OpenAIRE
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