Journal article
Cucurbitacin B inhibits human breast cancer cell proliferation through disruption of microtubule polymerization and nucleophosmin/B23 translocation
BMC complementary and alternative medicine, Vol.12(1), pp.185-185
10/12/2012
DOI: 10.1186/1472-6882-12-185
PMCID: PMC3527297
PMID: 23062075
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.
Details
- Title: Subtitle
- Cucurbitacin B inhibits human breast cancer cell proliferation through disruption of microtubule polymerization and nucleophosmin/B23 translocation
- Creators
- Suwit Duangmano - School of Allied Health Science and Public Health, Walailak University, Bangkok, ThailandPhorntip Sae-lim - Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, ThailandApichart Suksamrarn - Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, ThailandFrederick E Domann - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA, 52242, USAPimpicha Patmasiriwat - Faculty of Medical Technology, Mahidol University, Bangkok, Thailand
- Resource Type
- Journal article
- Publication Details
- BMC complementary and alternative medicine, Vol.12(1), pp.185-185
- DOI
- 10.1186/1472-6882-12-185
- PMID
- 23062075
- PMCID
- PMC3527297
- NLM abbreviation
- BMC Complement Altern Med
- ISSN
- 1472-6882
- eISSN
- 1472-6882
- Publisher
- BioMed Central
- Language
- English
- Date published
- 10/12/2012
- Academic Unit
- Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984046816202771
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