title: Pterocarpans induce tumor cell death through persistent mitotic arrest during prometaphase.
abstract: Pterocarpans, a family of isoflavonoids found in the diverse Fabaceae, display potent cytotoxic activity over a panel of tumor cell lines, and among those tested, 2,3,9- trimethoxypterocarpan displays the most potent activity. This study evaluates the effects of 2,3,9-trimethoxypterocarpan and its related derivatives on cell cycle progression and microtubule function in select breast cancer cell lines (MCF7, T47d and HS578T). The pterocarpans, with the exception of 3,4-dihydroxy-9-methoxipterocarpan, induced increased frequencies of mitotic cells by inducing arrest in prometaphase. While microtubule organization in interphase cells was not modified during treatment, mitotic cells exhibited high frequencies of monastral spindles surrounded by condensed chromosomes. Immunofluorescence staining with an anti-γ-tubulin antibody showed double-dot labeling in the spindle polar region, suggesting that pterocarpan treatment blocked centrosome segregation. We found that this mitotic arrest was reversible when the cells were treated for up to 24 h followed by recovery in drug-free medium, but not after 48-h treatment followed by incubation in drug-free medium. In that case, treated cells typically underwent cell multinucleation and apoptosis.
authors: Departamento de Fisiologia e Farmacologia, Universidade Federal de Pernambuco, CEP 50670-901 Recife, Ceará, Brazil.
authors: Gardenia C G
authors: GC
authors: Militão
authors: Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas I, Universidade de São Paulo, CP1524, CEP 05508-900 São Paulo, SP, Brazil.
authors: Marisa P
authors: MP
authors: Prado
authors: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, CEP 6430-270 Fortaleza, Ceará, Brazil.
authors: Cláudia
authors: C
authors: Pessoa
authors: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, CEP 6430-270 Fortaleza, Ceará, Brazil.
authors: Manoel Odorico
authors: MO
authors: de Moraes
authors: Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Caixa Postal-12200, 60021-940 Fortaleza, Ceará, Brazil.
authors: Edilberto R
authors: ER
authors: Silveira
authors: Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Caixa Postal-12200, 60021-940 Fortaleza, Ceará, Brazil.
authors: Mary Anne S
authors: MA
authors: Lima
authors: Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Caixa Postal-12200, 60021-940 Fortaleza, Ceará, Brazil.
authors: Pérsio Alexandrino
authors: PA
authors: Veloso
authors: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, CEP 6430-270 Fortaleza, Ceará, Brazil.
authors: Letícia V
authors: LV
authors: Costa-Lotufo
authors: Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas I, Universidade de São Paulo, CP1524, CEP 05508-900 São Paulo, SP, Brazil. Electronic address: glaucia.santelli@gmail.com.
authors: Gláucia M
authors: GM
authors: Machado-Santelli
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D049468:Prometaphase / Q000187:drug effects*; D011418:Prophase / Q000187:drug effects; D036343:Pterocarpans / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D036343:Pterocarpans
keywords: Apoptosis; Breast cancer cell lines; Cell cycle; Mitotic arrest; Pterocarpan