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Suberoylanilide hydroxamic acid as radiosensitizer through modulation of RAD51 protein and inhibition of homology-directed repair in multiple myeloma.
MedLine Citation:
PMID:  22729783     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Histone deacetylase inhibitors (HDIs) have shown promise as candidate radiosensitizers for many types of cancers. However, the mechanisms of action are not well understood, and whether they could sensitize multiple myeloma (MM) to radiation therapy is unclear. In this study, we demonstrate that Suberoylanilide hydroxamic acid (SAHA) at low concentrations has minimal cytotoxic effects, yet can significantly increase radiosensitivity of multiple myeloma (MM) cells. SAHA appears to block RAD51 protein response to ionizing radiation (IR), consistent with an inhibitory effect on the formation of RAD51 focus in irradiated MM cells. These effects of SAHA on RAD51 focus are independent of cell cycle distribution changes. Furthermore, we demonstrate that SAHA selectively inhibits the homology-directed repair (HDR) pathway. The results of this study suggest that SAHA, a recently approved HDI in clinical trials for malignancies, at lower concentrations may act as a radiosensitizer via disruption of the RAD51-dependent HDR pathway.
Authors:
Xufeng Chen; Patty Wong; Eric H Radany; Jeremy M Stark; Corentin Laulier; Jeffrey Y C Wong
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-22
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  -     ISSN:  1557-3125     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
City of Hope Medical Center.
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