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Inhibition of cell cycle and induction of apoptosis by 2‐oxoheksyl isothiocyanate and alyssin in cell lines carrying various inherited BRCA1 mutations
Authors:Irena Misiewicz  Agata Kozar  Katarzyna Skupinska  Elzbieta Kowalska  Jan Lubinski  Teresa Kasprzycka‐Guttman
Abstract:
An important aspect of the chemopreventive activity of isothiocyanates (ITC) is their ability to induce cell growth inhibition and apoptosis. In this study, the effect of two sulforaphane analogues, 2‐oxoheksyl isothiocyanate and alyssin, on lymphoblastoid cells, derived from people carrying four different germ‐line mutations in BRCA1 gene, was tested and compared to the effect on wild type cells. The mutations studied were: C61G; 3819del5; 4153delA, and 5382INSC. Changes in cell viability and density after 2‐oxoheksyl isothiocyanate and alyssin treatment were evaluated, as well as cell cycle progression, mitochondrial membrane potential changes, and phosphatidylserine externalization. Both isothiocyanates were shown to reduce cell viability and density in all cell lines tested, as well as the change in cell cycle phase's distribution. The response of cells to two ITC tested was various, as well as mutation type‐modulated. We found that change of cellular maintenance by chemopreventive agents can be modulated by single allele BRCA1 mutation. Drug Dev. Res. 65:84–92, 2005. © 2005 Wiley‐Liss, Inc.
Keywords:2‐oxoheksyl isothiocyanate  alyssin  isothiocyanates  BRCA1  chemoprevention  pharmacogenomics
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