Abstract
The effects of the novel vitamin D analogue, EB1089 alone, or in combination with the retinoid, 9-cis retinoic acid (9-cis RA) on indices of apoptosis in MCF-7 breast cancer cells have been examined. EB1089 was capable of reducing bcl-2 protein, a suppressor of apoptosis, and increasing p53 protein levels in MCF-7 cell cultures following 96h treatment. In the presence of 9-cis RA, EB1089 acted to further enhance the down-regulation and up-regulation of bcl-2 and p53 respectively. Furthermore, EB1089 induces DNA fragmentation in MCF-7 cells, a key feature of apoptosis, alone and in combination with 9-cis RA in situ. The observation that EB1089 and 9-cis RA act in a cooperative manner to enhance induction of apoptosis in these cells may have therapeutic implications.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / pathology*
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Apoptosis / drug effects*
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Breast Neoplasms / pathology*
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Calcitriol / analogs & derivatives*
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Calcitriol / pharmacology
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DNA Damage
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DNA, Neoplasm / analysis
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Drug Synergism
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neoplasms, Hormone-Dependent / pathology*
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-bcl-2
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Tretinoin / pharmacology*
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Tumor Cells, Cultured / drug effects
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Tumor Suppressor Protein p53 / biosynthesis
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Tumor Suppressor Protein p53 / genetics
Substances
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DNA, Neoplasm
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Neoplasm Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Protein p53
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Tretinoin
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Calcitriol
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seocalcitol