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Inhibition of aromatase activity and expression in MCF-7 cells by the chemopreventive retinoid N-(4-hydroxy-phenyl)-retinamide

  1. Author:
    Ciolino, H. P.
    Wang, T. T. Y.
    Sathyamoorthy, N.

  2. Author Address

    Ciolino HP NCI, Div Basic Sci, Basic Res Lab, Cellular Def & Carcinogenesis Sect,Frederick Canc Frederick, MD 21701 USA NCI, Div Basic Sci, Basic Res Lab, Cellular Def & Carcinogenesis Sect,Frederick Canc Frederick, MD 21701 USA USDA, Beltsville Human Nutr Res Ctr, Phytonutrients Lab Beltsville, MD 20705 USA NCI, Tumor Biol & Metastasis Branch Bethesda, MD 20892 USA
    1. Year: 2000
  2. Journal: British Journal of Cancer
    1. 83
    2. 3
    3. Pages: 333-337
  4. Type of Article: Article
  1. Abstract:

    The effect of the chemopreventive synthetic retinoid N-(4-hydroxyphenyl)-retinamide (4-HPR) on aromatase activity and expression was examined. 4-HPR caused a dose-dependent inhibition of aromatase activity in microsomes isolated from JEG-3 human placental carcinoma cells. The kinetics of inhibition were analysed by double-reciprocal plot. The Km of the substrate increased and the Vmax of the reaction decreased in the presence of 4-HPR, indicating that enzyme inhibition involved both competition for the substrate-binding site and non-competitive mechanisms. To determine whether 4-HPR would also inhibit aromatase activity in intact cells, MCF-7 human breast cancer cells were incubated with or without cAMP in the presence of 4-HPR. 4-HPR inhibited both basal and cAMP-induced aromatase activity in intact MCF-7 cells. The induction of aromatase mRNA expression in MCF-7 cells by cAMP was inhibited in cells treated with 4-HPR. These results indicate that 4-HPR inhibits both the enzymatic activity and expression of aromatase. These activities may play an important role in the known chemopreventive effect of 4-HPR towards breast cancer. (C) 2000 Cancer Research Campaign. [References: 32]

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