Inhibition of bladder cancer by broccoli isothiocyanates sulforaphane and erucin: characterization, metabolism, and interconversion
Abbaoui B, Riedl KM, Ralston RA, Thomas-Ahner JM, Schwartz SJ, Clinton SK, Mortazavi A
Molecular nutrition & food research · 70 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- National Cancer Institute
- Government
- National Institute of General Medical Sciences
- Government
- National Center for Complementary and Integrative Health
- Government
- NCI NIH HHS
- Government
- NIH/NCI OSU CCC
- Government
- NIH/NIGMS
- Government
- NCCIH NIH HHS
- Government
- NIH/NCCAM
- Government
- NIGMS NIH HHS
- University or hospital
- The Center for Functional Foods and Research Entrepreneurship (CAFFRE) Funds
- Nonprofit
- American Institute for Cancer Research (AICR) Grant
- University or hospital
- The Ohio State University Comprehensive Cancer Center Molecular Carcinogenesis and Chemoprevention Program
- Grants
- National Cancer Institute (P30CA016058); National Cancer Institute (P-30-CA-16058); National Institute of General Medical Sciences (T32GM068412); National Center for Complementary and Integrative Health (F31 AT006486); National Institute of General Medical Sciences (5T32GM068412-04)
Based on 12 listed funder(s).
Publication
- Published
- 2012-10-05 · Mol Nutr Food Res · vol. 56 · issue 11 · pp. 1675–1687
- Publisher
- Wiley
- Cited
- 105 citations · more than 93% of similar papers · 3.2× the field average
- Impact
- Top 10% most cited in its field
- References
- 51 works
- Access
- Open access (repository copy)
- Research areas
- Genomics, phytochemicals, and oxidative stress · Curcumin's Biomedical Applications · Garlic and Onion Studies
- Keywords
- Sulforaphane, Chemistry, Isothiocyanate, Cruciferous vegetables, Survivin, Glucosinolate, Bladder cancer, Apoptosis, Cancer research, Cancer, Cell growth, Biochemistry, Pharmacology, Internal medicine, Biology, Medicine, Brassica, Botany
- MeSH
- cell line, tumor, animals, humans, mice, mice, nude, brassica, sulfides, thiocyanates, isothiocyanates, sulfoxides, glucosinolates, plant extracts, anticarcinogenic agents, antineoplastic agents, phytogenic, xenograft model antitumor assays, apoptosis, female, inhibitor of apoptosis proteins, urinary bladder neoplasms, cell cycle checkpoints, erbb receptors, survivin, erb-b2 receptor tyrosine kinases
7 authors
From US
- Besma AbbaouiThe Ohio State University
- Kenneth M. RiedlThe Ohio State University
- Robin A. RalstonThe Ohio State University
- Jennifer M. Thomas‐AhnerThe Ohio State University
- Steven J. SchwartzThe Ohio State University
- Steven K. ClintonThe Ohio State University
Abstract
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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