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Pterocarpans induce tumor cell death through persistent mitotic arrest during prometaphase
Gardenia C G Militão1, Marisa P Prado2, Cláudia Pessoa3
1Departamento de Fisiologia e Farmacologia, Universidade Federal de Pernambuco, CEP 50670-901 Recife, Ceará, Brazil.
2,3,9-trimethoxypterocarpan, a potent isoflavonoid, halts breast cancer cell division by disrupting microtubule function and centrosome segregation. This effect is reversible within 24 hours but leads to cell death after 48 hours.
Area of Science:
- Natural Products Chemistry
- Cell Biology
- Cancer Research
Background:
- Pterocarpans, isoflavonoids from Fabaceae, exhibit significant cytotoxic effects.
- 2,3,9-trimethoxypterocarpan shows the highest potency among tested pterocarpans.
Purpose of the Study:
- To investigate the impact of 2,3,9-trimethoxypterocarpan and derivatives on cell cycle and microtubule function.
- To analyze effects on MCF7, T47d, and HS578T breast cancer cell lines.
Main Methods:
- Cell cycle analysis
- Microtubule organization assessment
- Immunofluorescence staining for γ-tubulin
Main Results:
- Pterocarpans induced prometaphase arrest in mitotic cells.
- Mitotic cells displayed abnormal monastral spindles and condensed chromosomes.
- Centrosome segregation was blocked, indicated by double-dot γ-tubulin labeling.
- Mitotic arrest was reversible after 24-hour treatment but led to multinucleation and apoptosis after 48 hours.
Conclusions:
- 2,3,9-trimethoxypterocarpan disrupts microtubule dynamics and centrosome function, leading to mitotic arrest in breast cancer cells.
- The duration of pterocarpan exposure determines the reversibility of mitotic arrest and subsequent cell fate (recovery or apoptosis).
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