Blockade of MUC1 Expression by Glycerol Guaiacolate Inhibits Proliferation of Human Breast Cancer Cells

    Authors

    J. S. Smith; J. Colon; R. Madero-Visbal; B. Isley; S. D. Konduri;C. H. Baker

    Comments

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    Abbreviated Journal Title

    Anti-Cancer Agents Med. Chem.

    Keywords

    Glycerol guaiacolate; MUC1; Breast cancer; RESPONSIVE ELEMENT; ESTROGEN-RECEPTOR; CARCINOMA-CELLS; GENE; MUCINS; ONCOPROTEIN; PROMOTER; SERUM; CONSERVATION; ANTIBODIES; Oncology; Chemistry, Medicinal

    Abstract

    We sought to determine whether administration of glycerol guaiacolate at an optimal biological dose inhibits human breast cancer cell growth. Human breast cancer MCF-7 and ZR-75-1 cells were treated with glycerol guaiacolate and the therapeutic efficacy and biological activity of this drug was investigated on breast cancer cell growth. MCF-7 cells were injected into the mammary fat pad of overectamized female athymic nude mice. Ten days later, animals were treated with daily intraperitoneal injections of glycerol guaiacolate for six weeks. Tumor size and volume was monitored and immunohistochemical analysis on MUC1, p21 and ki-67 was performed. Glycerol guaiacolate decreased breast cancer cell growth in a dose-dependent manner, decreased cell migration, and caused G1 cell cycle arrest. Our results demonstrate that glycerol guaiacolate inhibits MUC1 protein and mRNA expression levels and significantly increased p21 expression in human breast cancer cells as well as induced PARP cleavage. Similarly, glycerol guaiacolate inhibited breast tumor growth in vivo as well as enhanced p21 expression and decreased breast tumor cell proliferation (ki-67 expression). Collectively, our results demonstrate that glycerol guaiacolate decreased MUC1 expression and enhanced cell growth inhibition by inducing p21 expression in breast cancer cells. These findings suggest that glycerol guaiacolate may provide a novel and effective approach for the treatment of human breast cancer.

    Journal Title

    Anti-Cancer Agents in Medicinal Chemistry

    Volume

    10

    Issue/Number

    8

    Publication Date

    1-1-2010

    Document Type

    Article

    Language

    English

    First Page

    644

    Last Page

    650

    WOS Identifier

    WOS:000288318500008

    ISSN

    1871-5206

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