Open AccessInhibitory effect of nordihydroguaiaretic acid, a plant lignan, on Helicobacter pylori ‐associated gastric carcinogenesis in Mongolian gerbils
Author(s) -
Toyoda Takeshi,
Tsukamoto Tetsuya,
Mizoshita Tsutomu,
Nishibe Sansei,
Deyama Takeshi,
Takenaka Yoshiharu,
Hirano Naoki,
Tanaka Harunari,
Takasu Shinji,
Ban Hisayo,
Kumagai Toshiko,
Inada Kenichi,
Utsunomiya Hirotoshi,
Tatematsu Masae
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00599.x
Subject(s) - nordihydroguaiaretic acid , helicobacter pylori , in vivo , gastritis , genotoxicity , cancer , pharmacology , helicobacter , carcinogen , biology , stomach , intestinal metaplasia , chemistry , medicine , toxicity , biochemistry , lipoxygenase , microbiology and biotechnology , enzyme
Recent epidemiological studies have demonstrated that consumption of certain natural products can lower cancer risk in humans. For example, plant‐derived lignans have been shown to exert chemopreventive effects against cancer in vitro and in vivo . In the present study, the effects of three such lignans, termed arctiin, arctigenin, and nordihydroguaiaretic acid (NDGA), on the proliferation of Helicobacter pylori and the prevention of H. pylori ‐associated gastric cancer were investigated in Mongolian gerbils. To examine the effects of arctigenin and NDGA on stomach carcinogenesis, specific pathogen‐free male, 5‐week‐old gerbils were infected with H. pylori , administered 10 p.p.m. N ‐methyl‐ N ‐nitrosourea in their drinking water and fed diets containing various concentrations of lignans until they were killed after 52 weeks. At a dietary level of 0.25%, NDGA significantly decreased the incidence of gastric adenocarcinomas. Arctigenin, in contrast, failed to attenuate neoplasia at a level of 0.1%. Both NDGA and arctigenin significantly reduced serum 8‐hydroxy‐2′‐deoxyguanosine levels at doses of 0.25 and 0.05% (NDGA), and 0.1% (arctigenin). Administration of 0.25% NDGA significantly suppressed the formation of intestinal metaplasia both in the antrum and the corpus. Although all three lignans dose‐dependently inhibited the in vitro proliferation of H. pylori , there were no differences in the titers of anti‐ H. pylori antibodies or the amount of the H. pylori ‐specific urease A gene among all H. pylori ‐infected groups. These results suggest that NDGA might be effective for prevention of gastric carcinogenesis. The possible mechanisms appear to be related to inhibitory effects on progression of gastritis and antioxidative activity rather than direct antimicrobial influence. ( Cancer Sci 2007; 98: 1689–1695)