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      Retinoid N-(1H-benzo[d]imidazol-2-yl)-5,5,8,8-tetramethyl-5,6,7, 8-tetrahydronaphthalene-2-carboxamide induces p21-dependent senescence in breast cancer cells

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      Author(s)
      Mumcuoglu, M.
      Gurkan-Alp, A. S.
      Buyukbingol, E.
      Cetin Atalay, R.
      Date
      2016
      Source Title
      Steroids
      Print ISSN
      0039-128X
      Publisher
      Elsevier
      Volume
      108
      Pages
      31 - 38
      Language
      English
      Type
      Article
      Item Usage Stats
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      Abstract
      Retinoids have been implicated as pharmacological agents for the prevention and treatment of various types of cancers, including breast cancers. We analyzed 27 newly synthesized retinoids for their bioactivity on breast, liver, and colon cancer cells. Majority of the retinoids demonstrated selective bioactivity on breast cancer cells. Retinoid 17 had a significant inhibitory activity (IC50 3.5 μM) only on breast cancer cells while no growth inhibition observed with liver and colon cancer cells. The breast cancer selective growth inhibitory action by retinoid 17 was defined as p21-dependent cell death, reminiscent of senescence, which is an indicator of targeted receptor mediated bioactivity. A comparative analysis of retinoid receptor gene expression levels in different breast cancer cells and IC50 values of 17 indicated the involvement of Retinoid X receptors in the cytotoxic bioactivity of retinoid 17 in the senescence associated cell death. Furthermore, siRNA knockdown studies with RXRγ induced decrease in cell proliferation. Therefore, we suggest that retinoid derivatives that target RXRγ, can be considered for breast cancer therapies. © 2016 Elsevier Inc. All rights reserved.
      Keywords
      Breast cancer
      Cytotoxicity
      Retinoid
      RXR
      Senescence
      Permalink
      http://hdl.handle.net/11693/36772
      Published Version (Please cite this version)
      http://dx.doi.org/10.1016/j.steroids.2016.02.008
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