Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 56, Issue 11, Pages 1675-1687Publisher
WILEY
DOI: 10.1002/mnfr.201200276
Keywords
Bladder cancer; Broccoli; Erucin; Isothiocyanates; Sulforaphane
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Funding
- NIH/NCCAM [F31AT006486]
- NIH/NIGMS [5T32GM068412-04]
- NIH/NCI OSU CCC [P30 CA16058]
- American Institute for Cancer Research (AICR)
- Ohio State University Comprehensive Cancer Center Molecular Carcinogenesis and Chemoprevention Program
- Center for Functional Foods and Research Entrepreneurship (CAFFRE) Funds
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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 (IC50 = 5.66 +/- 1.2 mu M) and erucin (IC50 = 8.79 +/- 1.3 mu M) 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), G2/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 mu mol/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.
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