Publication: Cucurbitacin B inhibits human breast cancer cell proliferation through disruption of microtubule polymerization and nucleophosmin/B23 translocation
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Issued Date
2012
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eng
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Mahidol University
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BioMed Central
Bibliographic Citation
BMC Complementary and Alternative Medicine. Vol.12, (2012), 185
Suggested Citation
Suwit Duangmano, Phorntip Sae-lim, Apichart Suksamrarn, Frederick E Domann, Pimpicha Patmasiriwat Cucurbitacin B inhibits human breast cancer cell proliferation through disruption of microtubule polymerization and nucleophosmin/B23 translocation. BMC Complementary and Alternative Medicine. Vol.12, (2012), 185. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/2768
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Title
Cucurbitacin B inhibits human breast cancer cell proliferation through disruption of microtubule polymerization and nucleophosmin/B23 translocation
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Abstract
Background: Cucurbitacin B, an oxygenated tetracyclic triterpenoid compound extracted from the Thai medicinal
plant Trichosanthes cucumerina L., has been reported to have several biological activities including anti-inflammatory,
antimicrobial and anticancer. Cucurbitacin B is great of interest because of its biological activity. This agent inhibits
growth of various types of human cancer cells lines.
Methods: In this study, we explored the novel molecular response of cucurbitacin B in human breast cancer cells,
MCF-7 and MDA-MB-231. The growth inhibitory effect of cucurbitacin B on breast cancer cells was assessed by MTT
assay. The effects of cucurbitacin B on microtubules morphological structure and tubulin polymerization were analyzed
using immunofluorescence technique and tubulin polymerization assay kit, respectively. Proteomic analysis was used
to identify the target-specific proteins that involved in cucurbitacin B treatment. Some of the differentially expressed
genes and protein products were validated by real-time RT-PCR and western blot analysis. Cell cycle distributions and
apoptosis were investigated using flow cytometry.
Results: Cucurbitacin B exhibited strong antiproliferative effects against breast cancer cells in a dose-dependent
manner. We show that cucurbitacin B prominently alters the cytoskeletal network of breast cancer cells, inducing rapid
morphologic changes and improper polymerization of the microtubule network. Moreover, the results of
2D-PAGE, real-time RT-PCR, and western blot analysis revealed that the expression of nucleophosmin/B23 and c-Myc
decreased markedly after cucurbitacin B treatment. Immunofluorescence microscopy showed that cucurbitacin B
induced translocation of nucleophosmin/B23 from the nucleolus to nucleoplasm. Treatment with cucurbitacin B
resulted in cell cycle arrest at G2/M phase and the enhancement of apoptosis.
Conclusions: Our findings suggest that cucurbitacin B may inhibit the proliferation of human breast cancer cells
through disruption of the microtubule network and down-regulation of c-Myc and nucleophosmin/B23 as well as the
perturbation in nucleophosmin/B23 trafficking from the nucleolus to nucleoplasm, resulting in G2/M arrest.