Medical Sciences
Sulforaphane inhibits extracellular, intracellular, and
antibiotic-resistant strains of Helicobacter pylori
and prevents benzo[a]pyrene-induced stomach tumors
Jed W.
Fahey*,
,
,
Xavier
Haristoy§,
Patrick M.
Dolan¶,
Thomas W.
Kensler¶,
Isabelle
Scholtus§,
Katherine K.
Stephenson*,
Paul
Talalay*, and
Alain
Lozniewski§
* 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; 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, Faculté de
Médecine, 54505 Vandoeuvre-les-Nancy, France
Contributed by Paul Talalay, April 5, 2002
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 
4 µg/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.
To whom reprint requests should be addressed at:
Department of Pharmacology and Molecular Sciences, The Johns Hopkins
School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185. E-mail: jfahey{at}jhmi.edu.
