Document Detail

Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide.
MedLine Citation:
PMID:  20458559     Owner:  NLM     Status:  In-Data-Review    
Arsenic trioxide (As(2)O(3)), a component of traditional Chinese medicine, has been used successfully for the treatment of acute promyelocytic leukemia (APL), and As(2)O(3) is of potential therapeutic value for the treatment of other promyelocytic malignancies and some solid tumors including breast cancer. However, the precise molecular mechanisms through which As(2)O(3) induces cell cycle arrest and apoptosis in solid tumors have not been clearly understood. The goal of our study is to gain insight into the general biological processes and molecular functions that are altered by As(2)O(3) treatment in MCF-7 breast cancer cells and to identify the key signaling processes that are involved in the regulation of these physiological effects. In the present study, MCF-7 cells were treated with 5 μM As(2)O(3), and the differential gene expression was then analyzed by DNA microarray. The results showed that As(2)O(3) treatment changed the expression level of several genes that involved in cell cycle regulation, signal transduction, and apoptosis. Notably, As(2)O(3) treatment increased the mRNA and protein levels of the cell cycle inhibitory proteins, p21 and p27. Interestingly, knocking down p21 or p27 individually did not alter As(2)O(3)-induced apoptosis and cell cycle arrest; however, the simultaneous down-regulation of both p21 and p27 resulted in attenuating of G(1), G(2)/M arrest and reduction in apoptosis, thus indicating that p21 and p27 as the primary molecular targets of As(2)O(3) against breast cancer. Overall, our results provide new insights into As(2)O(3)-related signaling activities, which may facilitate the development of As(2)O(3)-based anticancer strategies and/or combination therapies against solid tumors.
Xi Wang; Ping Gao; Min Long; Fang Lin; Jun-Xia Wei; Ji-Hong Ren; Lin Yan; Ting He; Yuan Han; Hui-Zhong Zhang
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Publication Detail:
Type:  Journal Article     Date:  2010-05-11
Journal Detail:
Title:  Medical oncology (Northwood, London, England)     Volume:  28     ISSN:  1559-131X     ISO Abbreviation:  Med. Oncol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9435512     Medline TA:  Med Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1225-54     Citation Subset:  IM    
Research Center, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, 710038, Xi'an, Shaanxi Province, People's Republic of China.
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