title: 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.
authors: Center for Innovation Development and Technology Transfer, Faculty of Medical Technology, Mahidol University, Salaya, Nakhon Pathom, Thailand.
authors: Moltira
authors: M
authors: Promkan
authors: Sumana
authors: S
authors: Dakeng
authors: Subhas
authors: S
authors: Chakrabarty
authors: Oliver
authors: O
authors: Bögler
authors: Pimpicha
authors: P
authors: Patmasiriwat
mesh_terms: D019313:BRCA1 Protein / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D006801:Humans; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014315:Triterpenes; C041246:cucurbitacin B
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