Document Detail


Inhibition of bladder cancer by broccoli isothiocyanates sulforaphane and erucin: characterization, metabolism, and interconversion.
MedLine Citation:
PMID:  23038615     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
SCOPE: Epidemiologic evidence suggests diets rich in cruciferous vegetables, particularly broccoli, are associated with lower bladder cancer risk. Our objectives are to investigate these observations and determine the role of isothiocyanates in primary or secondary bladder cancer prevention.
METHODS AND RESULTS: We initially investigate the mechanisms whereby broccoli and broccoli sprout extracts and pure isothiocyanates inhibit normal, noninvasive (RT4), and invasive (J82, UMUC3) human urothelial cell viability. Sulforaphane (IC(50) = 5.66 ± 1.2 μM) and erucin (IC(50) = 8.79 ± 1.3 μM) are found to be the most potent inhibitors and normal cells are least sensitive. This observation is associated with downregulation of survivin, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2/neu), G(2) /M cell cycle accumulation, and apoptosis. In a murine UMUC3 xenograft model, we fed semipurified diets containing 4% broccoli sprouts, or 2% broccoli sprout isothiocyanate extract; or gavaged pure sulforaphane or erucin (each at 295 μmol/kg, similar to dietary exposure); and report tumor weight reduction of 42% (p = 0.02), 42% (p = 0.04), 33% (p = 0.04), and 58% (p < 0.0001), respectively. Sulforaphane and erucin metabolites are present in mouse plasma (micromolar range) and tumor tissue, with N-acetylcysteine conjugates as the most abundant. Interconversion of sulforaphane and erucin metabolites was observed.
CONCLUSION: This work supports development of fully characterized, novel food products containing broccoli components for phase I/II human studies targeting bladder cancer prevention.
Authors:
Besma Abbaoui; Kenneth M Riedl; Robin A Ralston; Jennifer M Thomas-Ahner; Steven J Schwartz; Steven K Clinton; Amir Mortazavi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-05
Journal Detail:
Title:  Molecular nutrition & food research     Volume:  56     ISSN:  1613-4133     ISO Abbreviation:  Mol Nutr Food Res     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-25     Completed Date:  2013-04-25     Revised Date:  2013-12-18    
Medline Journal Info:
Nlm Unique ID:  101231818     Medline TA:  Mol Nutr Food Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1675-87     Citation Subset:  IM    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticarcinogenic Agents / pharmacology*
Antineoplastic Agents, Phytogenic / pharmacology
Apoptosis / drug effects
Brassica / chemistry*,  growth & development,  metabolism
Cell Cycle Checkpoints / drug effects
Cell Line, Tumor
Female
Glucosinolates / analysis,  metabolism
Humans
Inhibitor of Apoptosis Proteins / metabolism
Isothiocyanates
Mice
Mice, Nude
Plant Extracts / chemistry,  pharmacology
Receptor, Epidermal Growth Factor / metabolism
Receptor, erbB-2 / metabolism
Sulfides / metabolism,  pharmacokinetics,  pharmacology*
Thiocyanates / metabolism,  pharmacokinetics,  pharmacology*
Urinary Bladder Neoplasms / metabolism,  pathology,  prevention & control*
Xenograft Model Antitumor Assays
Grant Support
ID/Acronym/Agency:
5T32GM068412-04/GM/NIGMS NIH HHS; F31 AT006486/AT/NCCAM NIH HHS; F31AT006486/AT/NCCAM NIH HHS; P30 CA016058/CA/NCI NIH HHS; P30 CA16058/CA/NCI NIH HHS; T32 GM068412/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Antineoplastic Agents, Phytogenic; 0/BIRC5 protein, human; 0/Glucosinolates; 0/Inhibitor of Apoptosis Proteins; 0/Isothiocyanates; 0/Plant Extracts; 0/Sulfides; 0/Thiocyanates; 4478-93-7/sulforafan; CTE370DL3U/erucin; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/ERBB2 protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.10.1/Receptor, erbB-2
Comments/Corrections

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