title: Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors.
abstract: Gastric infection with Helicobacter pylori is 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 of H. pylori within 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 of H. pylori [minimal inhibitory concentration (MIC) for 90% of the strains is <or=4 microg/ml], irrespective of their resistance to conventional antibiotics. Further, brief exposure to sulforaphane was bactericidal, and eliminated intracellular H. pylori from 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 the nrf2 gene, which regulates phase 2 enzymes. Thus, the dual actions of sulforaphane in inhibiting Helicobacter infections and blocking gastric tumor formation offer hope that these mechanisms might function synergistically to provide diet-based protection against gastric cancer in humans.
authors.affiliation: Lewis 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 21205-2185, USA. jfahey@jhmi.edu
authors.forename: Jed W
authors.initials: JW
authors.lastname: Fahey
authors.forename: Xavier
authors.initials: X
authors.lastname: Haristoy
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Dolan
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kensler
authors.forename: Isabelle
authors.initials: I
authors.lastname: Scholtus
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Stephenson
authors.forename: Paul
authors.initials: P
authors.lastname: Talalay
authors.forename: Alain
authors.initials: A
authors.lastname: Lozniewski
mesh_terms: D000363:Agaricales; D000658:Amoxicillin / Q000494:pharmacology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene; D001937:Brassica; D017291:Clarithromycin / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D005260:Female; D016480:Helicobacter pylori / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D006801:Humans; D017879:Isothiocyanates; D008795:Metronidazole / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D008517:Phytotherapy; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000382:microbiology / Q000517:prevention & control*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D008795:Metronidazole; D001564:Benzo(a)pyrene; D000658:Amoxicillin; C016766:sulforaphane; D017291:Clarithromycin