TRANSLATIONAL RESEARCH ON PREVENTION OF GASTROINTESTINAL CANCER BY SULFORAPHANE

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STUDY 1 Effec-Daiach: The isothiocyanate sulforaphane (SF) is abundant in broccoli sprouts in the form of its glucosinolate precursor (glucoraphanin). SF is powerfully bactericidal against Helicobacter pylori infections which are strongly associated with the worldwide pandemic of gastric cancer. Oral treatment with SF-rich broccoli sprouts of C57BL/6 mice infected with H. pylori SS1 and maintained on a high-salt (7.5% NaC1) diet reduced gastric bacterial colonization mitigated corpus inflammation, and prevented expression of high salt擁nduced gastric corpus atrophy. This therapeutic effect was not observed in mice in which the nrf2 gene was deleted, strongly implicating the important role of Nrf2-dependent antioxidant and anti-inflammatory proteins in SF-dependent protection. Forty-eight H. pylori-infected patients were randomly assigned to feeding of broccoli sprouts(BS) (70g daily; containing 420μmol of SF precursor) for 8 weeks or to consumption of an equal weight 〓 alfalfa sprouts(A … More S) (not containing SF) as placebo. Intervention with broccoli sprouts, but not with placebo, 〓creased the levels of urease measured by the urea breath test, and H. pylori stool antigen (biomarkers of H. pylori colonization) and serum pepsinogens (biomarkers of gastric inflammation). Values recovered to their original levels 2 months after treatment was discontinued. Daily intake of SF rich BS for 2 months reduces H. pylori colonization in mice and improves the sequelae of infection in infected mice and in humans. This treatment appears to enhance chemoprotection of the gastric mucosa against H. pylori-induced oxidative stress.STUDY 2 Effects on Colon: Wild type (nrf2+/+) and nrf2-gene knockout type (nrf2-/-) mice were treated for 7 days with 3% DSS, followed by 1% AOM. Mice were fed with or without BS, which contain 2.5 mmol SF. Mice were sacrificed at 8 wks after the treatment. In nrf2+/+, but not in nrf2-/- mice, treatment with BS attenuated DSS-induced colitis, and inhibited subsequent formation of ACF and colon tumors. These results show that daily intake of sulforaphane羊ich broccoli sprouts improves DSS擁nduced colitis and inhibits colon tumor formation induced by DSS+AOM. Our data further suggest that a diet rich in sulforaphane glucosinolate may be useful in Less