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.
journal_name
Biochimiejournal_title
Biochimieauthors
Militão GC,Prado MP,Pessoa C,de Moraes MO,Silveira ER,Lima MA,Veloso PA,Costa-Lotufo LV,Machado-Santelli GMdoi
10.1016/j.biochi.2014.06.005subject
Has Abstractpub_date
2014-09-01 00:00:00pages
147-55eissn
0300-9084issn
1638-6183pii
S0300-9084(14)00148-5journal_volume
104pub_type
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