A Rationally Designed Genotoxin that Selectively Destroys Estrogen Receptor-Positive Breast Cancer Cells
2002; American Chemical Society; Volume: 124; Issue: 9 Linguagem: Inglês
10.1021/ja017344p
ISSN1943-2984
AutoresKaushik Mitra, John C. Marquis, Shawn Hillier, Peter T. Rye, Beatriz Zayas, Annie S. Lee, John M. Essigmann, Robert G. Croy,
Tópico(s)Carcinogens and Genotoxicity Assessment
ResumoWe describe a novel strategy to increase the selective toxicity of genotoxic compounds. The strategy involves the synthesis of bifunctional molecules capable of forming DNA adducts that have high affinity for specific proteins in target cells. It is proposed that the association of such proteins with damaged sites in DNA can compromise protein function and/or DNA repair resulting in increased toxicity. We describe the synthesis of a bifunctional compound consisting of an aniline mustard linked to the 7α position of estradiol. This novel compound can form covalent DNA adducts that have high affinity for the estrogen receptor. Breast cancer cells that express high levels of the estrogen receptor showed increased sensitivity to the cytotoxic effects of the new compound.
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