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The effectiveness of cucurbitacin B in BRCA1 defective breast cancer cells.

Abstract
Cucurbitacin B (CuB) is one of the potential agents for long term anticancer chemoprevention. Cumulative evidences has shown that cucurbitacin B provides potent cellular biological activities such as hepatoprotective, anti-inflammatory and antimicrobial effects, but the precise mechanism of this agent is not clearly understood. We examine the biological effects on cancer cells of cucurbitacin B extracted from a Thai herb, Trichosanthes cucumerina L. The wild type (wt) BRCA1, mutant BRCA1, BRCA1 knocked-down and BRCA1 overexpressed breast cancer cells were treated with the cucurbitacin B and determined for the inhibitory effects on the cell proliferation, migration, invasion, anchorage-independent growth. The gene expressions in the treated cells were analyzed for p21/(Waf1), p27(Kip1) and survivin. Our previous study revealed that loss of BRCA1 expression leads to an increase in survivin expression, which is responsible for a reduction in sensitivity to paclitaxel. In this work, we showed that cucurbitacin B obviously inhibited knocked-down and mutant BRCA1 breast cancer cells rather than the wild type BRCA1 breast cancer cells in regards to the cellular proliferation, migration, invasion and anchorage-independent growth. Furthermore, forcing the cells to overexpress wild type BRCA1 significantly reduced effectiveness of cucurbitacin B on growth inhibition of the endogenous mutant BRCA1 cells. Interestingly, cucurbitacin B promotes the expression of p21/(Waf1) and p27(Kip1) but inhibit the expression of survivin. We suggest that survivin could be an important target of cucurbitacin B in BRCA1 defective breast cancer cells.
AuthorsMoltira Promkan, Sumana Dakeng, Subhas Chakrabarty, Oliver Bögler, Pimpicha Patmasiriwat
JournalPloS one (PLoS One) Vol. 8 Issue 2 Pg. e55732 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID23393598 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • BRCA1 Protein
  • BRCA1 protein, human
  • Triterpenes
  • cucurbitacin B
Topics
  • BRCA1 Protein (metabolism)
  • Blotting, Western
  • Breast Neoplasms (metabolism)
  • Cell Line, Tumor
  • Cell Movement (drug effects, genetics)
  • Cell Survival (drug effects, genetics)
  • Humans
  • Triterpenes (pharmacology)

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