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BU-32: a novel proteasome inhibitor for breast cancer
Breast Cancer Research, 10/15/09

Agyin JK et al. – This study shows that BU-32 is effective in cultured breast cancer cells and in breast cancer xenografts. The results suggest its potential benefit in breast cancer treatment.

• Synthesized a novel proteasome inhibitor (BU-32) and tested its growth inhibitory effects in different breast cancer cells including MCF-7, MDA-MB-231, and SKBR3 by in vitro cytotoxicity and proteasomal inhibition assays
• Apoptotic potential of BU-32 tested using flow cytometry and analyzing cell cycle regulatory proteins
• In vivo tumor xenograft studies for solid tumor as well as tumor metastasis conducted using MDA-MB-231-GFP cells

• BU-32 exhibits strong cytotoxicity in panel of cell lines - MDA-MB-231 , SKBR3 and MCF-7 cells
• BU-32 down-regulates a wide array of angiogenic marker genes and up-regulates apoptotic markers, including Bid and Bax
• Incubation of MDA-MB-231 cells with BU-32 results in accumulation of cell cycle inhibitor proteins p21 and P27 and stabilization of tumor suppressor protein p53
• Studies in in vivo solid tumor and metastasis models show significant effect with 0.06 mg/kg dose of BU-32 and marked reduction in tumor burden in skeleton

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