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  • [Mol Pharm.] Targeted Lipid Nanoemulsions Encapsulating Epigenetic Drugs Exhibit Selective Cytotoxicity on CDH1-/FOXM1+ Triple Negative Breast Cancer Cells.

    The City College of New York / 김범준, Debra T. Auguste*

  • 출처
    Mol Pharm.
  • 등재일
    2019 May 6
  • 저널이슈번호
    16(5):1813-1826. doi: 10.1021/acs.molpharmaceut.8b01065. Epub 2019 Mar 29.
  • 내용

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    Abstract
    The plasticity of cancer epigenetics makes them plausible candidates for therapeutic intervention. We took advantage of elevated expression of lysophosphatidic acid receptor 1 (LPAR1) in triple negative breast cancer (TNBC) tissues to target decitabine (DAC) and panobinostat (PAN) to breast cancer cells. DAC and PAN were shown to reverse abnormal methylation of DNA and altered chromatin structure, respectively, leading to increased expression of tumor suppressor genes and decreased expression of oncogenes. Although DAC and PAN have therapeutic benefits, they are limited by chemical instability and systemic toxicity. Herein, we present LPAR1-targeted, lipid nanoemulsions (LNEs) encapsulating both DAC and PAN. Our results demonstrated that the cell uptake and in vivo biodistribution of LNEs was dependent on LPAR1 expression in TNBCs. DAC/PAN-LNEs were effective in inhibiting the growth of mesenchymal breast cancer cells by restoring CDH1/E-cadherin and suppressing forkhead box M1 (FOXM1) expression. Epithelial breast cancer cells that inherently express low FOXM1 and high CDH1 were unaffected by DAC/PAN-LNEs. Overall, we successfully designed LPAR1-targeted LNEs that selectively act on CDH1(low)/FOXM1(high) TNBC cell lines.

     


    Author information

    Kim B1, Pena CD1, Auguste DT1.
    1
    Department of Biomedical Engineering , The City College of New York , 160 Convent Avenue , New York , New York 10031 , United States.

  • 키워드
    CDH1; FOXM1; LPA, LPAR1; decitabine; epigenetic; lipid nanoemulsion; panobinostat; triple negative breast cancer
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