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 citas
Cómo se estudió
- Diseño
- Estudio en animales (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- National Cancer Institute
- Gobierno
- National Institute of General Medical Sciences
- Gobierno
- National Center for Complementary and Integrative Health
- Gobierno
- NCI NIH HHS
- Gobierno
- NIH/NCI OSU CCC
- Gobierno
- NIH/NIGMS
- Gobierno
- NCCIH NIH HHS
- Gobierno
- NIH/NCCAM
- Gobierno
- NIGMS NIH HHS
- Universidad u hospital
- The Center for Functional Foods and Research Entrepreneurship (CAFFRE) Funds
- Organización sin fines de lucro
- American Institute for Cancer Research (AICR) Grant
- Universidad u hospital
- The Ohio State University Comprehensive Cancer Center Molecular Carcinogenesis and Chemoprevention Program
- Subvenciones
- 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)
Según 12 financiadores declarados.
Publicación
- Publicado
- 2012-10-05 · Mol Nutr Food Res · vol. 56 · número 11 · págs. 1675–1687
- Editorial
- Wiley
- Citado
- 105 citas · más que el 93% de estudios similares · 3.2× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 51 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Genomics, phytochemicals, and oxidative stress · Curcumin's Biomedical Applications · Garlic and Onion Studies
- Palabras clave
- 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 autores
- Besma Abbaoui🇺🇸The Ohio State University
- Kenneth M. Riedl🇺🇸The Ohio State University
- Robin A. Ralston🇺🇸The Ohio State University
- Jennifer M. Thomas‐Ahner🇺🇸The Ohio State University
- Steven J. Schwartz🇺🇸The Ohio State University
- Steven K. Clinton🇺🇸The Ohio State University
- Amir Mortazavi🇺🇸 · autor de correspondenciaThe Ohio State University
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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