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1,1-Bis(3′-indolyl)-1-(p-substituted phenyl)methanes inhibit proliferation of estrogen receptor-negative breast cancer cells by activation of multiple pathways

Vanderlaag, Kathy ; Su, Yunpeng ; Frankel, Arthur E. ; Grage, Henry ; Smith, Roger ; Khan, Shaheen ; Safe, Stephen

Breast cancer research and treatment, 2008-05, Vol.109 (2), p.273-283 [Periódico revisado por pares]

Boston: Springer US

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Título:
1,1-Bis(3′-indolyl)-1-(p-substituted phenyl)methanes inhibit proliferation of estrogen receptor-negative breast cancer cells by activation of multiple pathways
Autor: Vanderlaag, Kathy ; Su, Yunpeng ; Frankel, Arthur E. ; Grage, Henry ; Smith, Roger ; Khan, Shaheen ; Safe, Stephen
Assuntos: Animals ; Antineoplastic Agents - pharmacology ; Biological and medical sciences ; Blotting, Western ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Cancer ; Cancer cells ; Cancer research ; Cancer therapies ; Care and treatment ; Cell cycle ; Cell growth ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cytokines - drug effects ; Cytokines - metabolism ; Enzyme Activation - drug effects ; Estrogen ; Female ; Flow Cytometry ; Growth Differentiation Factor 15 ; Gynecology. Andrology. Obstetrics ; Humans ; Indoles - pharmacology ; Kinases ; Mammary gland diseases ; Medical sciences ; Medicine ; Medicine & Public Health ; Methane ; Mice ; Mice, Nude ; Oncology ; Phenols ; PPAR gamma - antagonists & inhibitors ; Preclinical Study ; Prevention ; Protein Kinases - drug effects ; Protein Kinases - metabolism ; Receptors, Estrogen - metabolism ; Signal transduction ; Signal Transduction - drug effects ; Transfection ; Tumors ; Xenograft Model Antitumor Assays
É parte de: Breast cancer research and treatment, 2008-05, Vol.109 (2), p.273-283
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: 1,1-Bis(3′-indolyl)-1-( p -substituted phenyl)methanes containing para -trifluoromethyl (DIM-C-pPhCF 3 ), t -butyl (DIM-C-pPhtBu), and phenyl (DIM-C-pPhC 6 H 5 ) groups are methylene-substituted diindolylmetyhanes (C-DIMs) that activate peroxisome proliferator-activated receptor γ (PPARγ) in estrogen receptor α-negative MDA-MB-231 and MDA-MB-453 breast cancer cells. C-DIMs inhibit breast cancer cell proliferation; however, inhibition of G 0 /G 1 to S phase progression and cyclin D1 downregulation was observed in MDA-MB-231 but not MDA-MB-453 cells. Nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1), a transforming growth factor β-like peptide, was also induced by these compounds, and the response was dependent on cell-context dependent activation of kinase pathways. However, inhibition of cell growth, induction of NAG-1 and activation of kinases by C-DIMs were not inhibited by PPARγ antagonists. Despite the induction of NAG-1 and downregulation of the antiapoptotic protein survivin by C-DIMs in both MDA-MB-231 and MDA-MB-453 cells, apoptotic cell death was not observed. Nevertheless, the cytotoxicity of C-DIMs in vitro was complemented by inhibition of tumor growth in athymic nude mice bearing MDA-MB-231 cells as xenografts and treated with DIM-C-pPhC 6 H 5 (40 mg/kg/day). The growth inhibition of tumors derived from highly aggressive MDA-MB-231 cells suggests a potential role for the C-DIM compounds in the clinical treatment of ER-negative breast cancer.
Editor: Boston: Springer US
Idioma: Inglês

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1,1-Bis(3′-indolyl)-1-(p-substituted phenyl)methanes inhibit proliferation of estrogen receptor-negative breast cancer cells by activation of multiple pathways

Vanderlaag, Kathy ; Su, Yunpeng ; Frankel, Arthur E. ; Grage, Henry ; Smith, Roger ; Khan, Shaheen ; Safe, Stephen

Boston: Springer US

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