Document Detail


Pomegranate extract induces apoptosis in human prostate cancer cells by modulation of the IGF-IGFBP axis.
MedLine Citation:
PMID:  19853487     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The IGF axis is critical for the regulation of apoptosis in many human cancer cell lines. Recently, potent anti-tumorigenic effects of pomegranate juice and extracts have been reported. Consequently, pomegranate has potential not only as a treatment but also as a preventative measure against certain types of cancer, including prostate. In this study, we investigated the relationship between pomegranate-induced apoptosis in human prostate cancer cells and the IGF/IGFBP system. Treatment of LAPC4 prostate cancer cells with 10microg/ml POMx, a highly potent pomegranate extract prepared from skin and arils minus seeds and standardized to ellagitannin content (37% punicalagins by HPLC), resulted in inhibition of cell proliferation and induction of apoptosis. Interestingly, co-treatment with POMx and IGFBP-3 revealed synergistic stimulation of apoptosis and additive inhibition of cell growth. Western blot analysis revealed that treatment with POMx or POMx/IGFBP-3 combination resulted in increased JNK phosphorylation, and decreased Akt and mTOR activation, consistent with a growth inhibitory, pro-apoptotic function. We also investigated the relationship between IGF-1 and pomegranate-induced apoptosis in 22RV1 prostate cancer cells. Co-treatment with 100ng/ml IGF-1 completely blocked apoptosis induction by POMx. In contrast, IGF-I failed to inhibit POMx-induced apoptosis in R(-) cells, suggesting the importance of IGF-IR. POMx-treatment decreased Igf1 mRNA expression in a dose-dependent manner indicating that its actions also involve tumor-specific suppression of IGF-1. These studies revealed novel interactions between the IGF system and pomegranate-induced apoptosis.
Authors:
Satomi Koyama; Laura J Cobb; Hemal H Mehta; Navindra P Seeram; David Heber; Allan J Pantuck; Pinchas Cohen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-10-22
Journal Detail:
Title:  Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society     Volume:  20     ISSN:  1532-2238     ISO Abbreviation:  Growth Horm. IGF Res.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-04-09     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  9814320     Medline TA:  Growth Horm IGF Res     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  55-62     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / chemistry,  pharmacology*
Apoptosis*
Cell Line, Tumor
Cell Proliferation / drug effects
Humans
Hydrolyzable Tannins / analysis,  pharmacology
Insulin-Like Growth Factor Binding Protein 3 / metabolism*
Insulin-Like Growth Factor I / metabolism*
Intracellular Signaling Peptides and Proteins / drug effects
JNK Mitogen-Activated Protein Kinases / drug effects
Male
Plant Extracts / chemistry,  pharmacology*
Prostatic Neoplasms / metabolism*
Protein-Serine-Threonine Kinases / drug effects
Punicaceae / chemistry*
TOR Serine-Threonine Kinases
Grant Support
ID/Acronym/Agency:
1R01CA100938/CA/NCI NIH HHS; P50 CA092131/CA/NCI NIH HHS; P50 CA092131-01A10003/CA/NCI NIH HHS; P50 CA092131-08/CA/NCI NIH HHS; P50CA92131/CA/NCI NIH HHS; R01 AG020954/AG/NIA NIH HHS; R01 AG020954-04/AG/NIA NIH HHS; R01 CA100938/CA/NCI NIH HHS; R01 CA100938-05/CA/NCI NIH HHS; R01HD047013/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Hydrolyzable Tannins; 0/Insulin-Like Growth Factor Binding Protein 3; 0/Intracellular Signaling Peptides and Proteins; 0/Plant Extracts; 0/ellagitannin; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases
Comments/Corrections

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