Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains ofHelicobacter pyloriand prevents benzo[a]pyrene-induced stomach tumors

Proceedings of the National Academy of Sciences of the United States of America - Tập 99 Số 11 - Trang 7610-7615 - 2002
Jed W. Fahey1, X. Haristoy1, Patrick M. Dolan1, Thomas W. Kensler1, Isabelle Scholtus1, Katherine K. Stephenson1, Paul Talalay1, Alain Lozniewski1
1Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205; Center for Human Nutrition, and Department of Environmental Health Sciences, The Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205; and Laboratoire de Bactériologie-Virologie, Unité Mixte de Recherche, Centre National de la Recherche Scientifique 75-65,...

Tóm tắt

Gastric infection withHelicobacter pyloriis a cosmopolitan problem, and is especially common in developing regions where there is also a high prevalence of gastric cancer. These infections are known to cause gastritis and peptic ulcers, and dramatically enhance the risk of gastric cancer. Eradication of this organism is an important medical goal that is complicated by the development of resistance to conventional antimicrobial agents and by the persistence of a low level reservoir ofH. pyloriwithin gastric epithelial cells. Moreover, economic and practical problems preclude widespread and intensive use of antibiotics in most developing regions. We have found that sulforaphane [(−)-1-isothiocyanato-(4R)-(methylsulfinyl)butane], an isothiocyanate abundant as its glucosinolate precursor in certain varieties of broccoli and broccoli sprouts, is a potent bacteriostatic agent against 3 reference strains and 45 clinical isolates ofH. pylori[minimal inhibitory concentration (MIC) for 90% of the strains is ≤4 μg/ml], irrespective of their resistance to conventional antibiotics. Further, brief exposure to sulforaphane was bactericidal, and eliminated intracellularH. pylorifrom a human epithelial cell line (HEp-2). In complementary experiments, sulforaphane blocked benzo[a]pyrene-evoked forestomach tumors in ICR mice. This protection resulted from induction of phase 2 detoxication and antioxidant enzymes, and was abrogated in mice lacking thenrf2gene, which regulates phase 2 enzymes. Thus, the dual actions of sulforaphane in inhibitingHelicobacterinfections and blocking gastric tumor formation offer hope that these mechanisms might function synergistically to provide diet-based protection against gastric cancer in humans.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 99 Số 11

7610-7615

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