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Anti-breast Cancer Effects of Histone Deacetylase Inhibitors and Calpain Inhibitor.
MedLine Citation:
PMID:  22753709     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Development of new breast cancer therapies is needed, particularly as cells become refractory or develop increased drug resistance. In an effort to develop such treatments, class I and II histone deacetylases (HDACs), alone and in combination with other cytotoxic agents, are currently in clinical trial. Herein, we discuss the effects of histone deacetylase inhibitors (HDACi) when used in combination with calpeptin, an inhibitor of the regulatory protease, calpain. We present results of study in two breast cancer cells lines with distinct characteristics: MDA-MB-231 and MCF-7. When used in combination with calpeptin, two chemically distinct HDACi significantly inhibited growth and increased cell death by inducing cell-cycle arrest and apoptosis. MCF-7 cells exhibited a greater proportion of arrest at the G(1) phase, whereas triple-negative MDA-MB-231 cells exhibited increased cell cycle arrest at the S phase. Methylation of the imprinted and silenced proapoptoic tumor suppressor gene aplasia Ras homolog member I (ARHI) was reduced in both cell lines after treatment with HDACi. However, it was only re-expressed on such treatment in MDA-MB-231 cells, suggesting that re-expression operates under differential mechanisms in these two cell lines. Collectively, these results showed that the combination of HDACi and calpeptin inhibited the growth of two distinctly different types of breast cancer cells and could have wide clinical applications, though the mechanisms of inhibition are possibly different.
Authors:
Megan A Mataga; Shoshana Rosenthal; Sarah Heerboth; Amrita Devalapalli; Shannon Kokolus; Leah R Evans; McKenna Longacre; Genevieve Housman; Sibaji Sarkar
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  32     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  2523-9     Citation Subset:  IM    
Affiliation:
Cancer Center, Boston University School of Medicine, 72 East Concord Street, L-913, Boston, MA 02118, U.S.A. ss1@bu.edu.
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