Document Detail


3,3'-Diindolylmethane downregulates pro-survival pathway in hormone independent prostate cancer.
MedLine Citation:
PMID:  16380095     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epidemiological evidences suggest that the progression and promotion of prostate cancer (CaP) can be modulated by diet. Since all men die with prostate cancer rather than of the disease, it is of particular interest to prevent or delay the progression of the disease by chemopreventive strategies. We have been studying the anticancer properties of compounds present in cruciferous vegetables such as indole-3-carbinol (I3C). Diindolylmethane (DIM) is a dimer of I3C that is formed under acidic conditions and unlike I3C is more stable with higher anti-cancer effects. In the present report, we demonstrate that DIM is a potent anti-proliferative agent compared to I3C in the hormone independent DU 145 CaP cells. The anti-prostate cancer effect is mediated by the inhibition of the Akt signal transduction pathway as DIM, in sharp contrast to I3C, induces the downregulation of Akt, p-Akt, and PI3 kinase. DIM also induced a G1 arrest in DU 145 cells by flow cytometry and downstream concurrent inhibition of cell cycle parameters such as cyclin D1, cdk4, and cdk6. Our data suggest a need for further development of DIM, as a chemopreventive agent for CaP, which justifies epidemiological evidences and molecular targets that are determinants for CaP dissemination/progression. The ingestion of DIM may benefit CaP patients and reduce disease recurrence by eliminating micro-metastases that may be present in patients who undergo radical prostatectomy.
Authors:
Venkata P S Garikapaty; Badithe T Ashok; Kiranmayi Tadi; Abraham Mittelman; Raj K Tiwari
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2005-12-20
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  340     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-03     Completed Date:  2006-03-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  718-25     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors
Androgens / physiology*
Anticarcinogenic Agents / pharmacology*
Apoptosis / drug effects
Biological Markers
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects,  physiology
DNA Replication / drug effects
Down-Regulation / drug effects*
G1 Phase / drug effects
Growth Inhibitors / pharmacology*
Humans
Indoles / pharmacology*
Male
Prostatic Neoplasms / drug therapy*,  pathology
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
S Phase / drug effects
Signal Transduction / drug effects*,  physiology
Grant Support
ID/Acronym/Agency:
CA29502/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Androgens; 0/Anticarcinogenic Agents; 0/Biological Markers; 0/Growth Inhibitors; 0/Indoles; 1968-05-4/3,3'-diindolylmethane; 700-06-1/indole-3-carbinol; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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