【摘 要】
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Breast cancer is a major killer of women world wide.Every year, 1,000,000 new cases are diagnosed, with 40,000 deaths in the United States.Many patients either do not respond to chemotherapy or lose t
【机 构】
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Department of Anatomy and Cell Biology University of Saskatchewan Canada
【出 处】
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(BITs 3rd Annual World Cancer Congress-2010, Breast Cancer C
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Breast cancer is a major killer of women world wide.Every year, 1,000,000 new cases are diagnosed, with 40,000 deaths in the United States.Many patients either do not respond to chemotherapy or lose their initial responsiveness.We have shown that a combination of Troglitazone (TRG) and Doxorubicin (DOX) effectively kills multiple drug resistant K562 leukemia and MCF7 breast cancer cells.TRG treatment reduced the expression ofMDR-1 and BCRP in drug resistant MCF7 cells, which was associated with increased histone H3K9, K14 and K23 acetylation and H3K79 mono-and dimethylation.TRG and multiple histone deacetylase inhibitors (HDACis) induced the same histone posttranslational modifications (PTMs), suggesting that TRG may have HDACi activity.Indeed, TRG inhibited HDAC activity in treated whole cell lysates and ceils.This provides a molecular mechanism for TRGs antiproliferative activity,as HDACis are known anticancer agents.We propose that mechanisms that alter epigenetic structure, leading to increased global transcription, such as the case with HDACis, would provide a mechanism for killing cancer cells.
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