Document Detail


Targeted regulation of PI3K/Akt/mTOR/NF-κB signaling by indole compounds and their derivatives: mechanistic details and biological implications for cancer therapy.
MedLine Citation:
PMID:  23272910     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Indole compounds, found in cruciferous vegetables, are potent anti-cancer agents. Studies with indole-3-carbinol (I3C) and its dimeric product, 3,3'-diindolylmethane (DIM) suggest that these compounds have the ability to deregulate multiple cellular signaling pathways, including PI3K/Akt/mTOR signaling pathway. These natural compounds are also effective modulators of downstream transcription factor NF-κB signaling which might help explain their ability to inhibit invasion and angiogenesis, and the reversal of epithelial-to-mesenchymal transition (EMT) phenotype and drug resistance. Signaling through PI3K/Akt/mTOR and NF-κB pathway is increasingly being realized to play important role in EMT through the regulation of novel miRNAs which further validates the importance of this signaling network and its regulations by indole compounds. Here we will review the available literature on the modulation of PI3K/Akt/mTOR/NF-κB signaling by both parental I3C and DIM, as well as their analogs/derivatives, in an attempt to catalog their anticancer activity.
Authors:
Aamir Ahmad; Bernhard Biersack; Yiwei Li; Dejuan Kong; Bin Bao; Rainer Schobert; Subhash B Padhye; Fazlul H Sarkar
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Anti-cancer agents in medicinal chemistry     Volume:  13     ISSN:  1875-5992     ISO Abbreviation:  Anticancer Agents Med Chem     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-07-29     Completed Date:  2014-02-13     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  101265649     Medline TA:  Anticancer Agents Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1002-13     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents, Phytogenic / chemistry,  pharmacology,  therapeutic use*
Humans
Indoles / chemistry,  pharmacology,  therapeutic use*
Molecular Targeted Therapy / methods
NF-kappa B / metabolism*
Neoplasms / drug therapy*,  metabolism,  pathology
Phosphatidylinositol 3-Kinases / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction / drug effects
TOR Serine-Threonine Kinases / metabolism*
Grant Support
ID/Acronym/Agency:
R01 CA108535/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Indoles; 0/NF-kappa B; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections

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


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