Document Detail

3,3'-Diindolylmethane negatively regulates Cdc25A and induces a G2/M arrest by modulation of microRNA 21 in human breast cancer cells.
MedLine Citation:
PMID:  20724916     Owner:  NLM     Status:  MEDLINE    
3,3'-Diindolylmethane (DIM) is a potential chemopreventive phytochemical derived from Brassica vegetables. In this study, we assessed the effects of DIM on cell cycle regulation in both estrogen-dependent MCF-7 and estrogen receptor negative p53 mutant MDA-MB-468 human breast cancer cells. In-vitro culture studies showed that DIM dose dependently inhibited the proliferation of both cells. In addition, in-vivo xenograft model showed that DIM strongly inhibited the development of human breast tumors. Fluorescence activated cell sorter analysis showed a DIM-mediated G2/M cell cycle arrest in MCF-7 and MDA-MB-468 cells. Western blot analysis showed that DIM downregulated the expression of cyclin-dependent kinases 2 and 4 and Cdc25A, which plays an important role in G2/M phase. Furthermore, treatment of MCF-7 cells with DIM, which increased microRNA 21 expression, caused a downregulation of Cdc25A, resulting in an inhibition of breast cancer cell proliferation. Taken together, our data show that DIM is able to stop the cell cycle progression of human breast cancer cells regardless of their estrogen-dependence and p53 status, by differentially modulating cell cycle regulatory pathways. The modulation of microRNA 21 mediates the DIM cell cycle regulator effect in MCF-7 cells.
Yucui Jin; Xianghong Zou; Xiaoling Feng
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Retracted Publication    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  21     ISSN:  1473-5741     ISO Abbreviation:  Anticancer Drugs     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-02     Completed Date:  2010-12-22     Revised Date:  2011-03-07    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  814-22     Citation Subset:  IM    
Capital Normal University, Beijing, China.
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MeSH Terms
Anticarcinogenic Agents / administration & dosage,  pharmacology
Antineoplastic Agents / administration & dosage,  pharmacology*
Blotting, Western
Breast Neoplasms / drug therapy*,  pathology
Cell Division / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
G2 Phase / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Indoles / administration & dosage,  pharmacology*
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / metabolism*
Xenograft Model Antitumor Assays
cdc25 Phosphatases / drug effects,  genetics
Grant Support
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Antineoplastic Agents; 0/Indoles; 0/MicroRNAs; 0/mirn21 microRNA, rat; 1968-05-4/3,3'-diindolylmethane; EC protein, human; EC Phosphatases
Retraction In:
Anticancer Drugs. 2011 Mar;22(3):303   [PMID:  21282984 ]

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