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Inhibition of N'-nitrosonornicotine-induced esophageal tumorigenesis by 3-phenylpropyl isothiocyanate
G D Stoner1, C Adams, L A Kresty
1Division of Environmental Health Sciences, The Ohio State University School of Public Health and The Ohio State University Comprehensive Cancer Center, Ohio State University, CHRI, Columbus 43210, USA. stoner.21@osu.edu
Abstract:
The ability of dietary isothiocyanates to inhibit the esophageal metabolism of N'-nitrosonornicotine (NNN) was examined in F344 rats. Following feeding of benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), 3-phenylpropyl isothiocyanate (PPITC), 4-phenylbutyl isothiocyanate (PBITC) or 6-phenylhexyl isothiocyanate for 2 weeks, rats were killed and the esophagi were incubated in vitro with [5-3H]NNN. While dietary BITC, PEITC and PBITC all decreased NNN metabolism, dietary PPITC had the greatest effect, yielding inhibition ranging from 55 to 91% of the control production of various NNN metabolites. To determine the chemopreventive efficacy of PPITC on NNN-induced esophageal tumorigenesis, rats were fed AIN-76A diets containing 0, 1.0 or 2.5 micromol/g PPITC and were given untreated drinking water or drinking water containing 5 p.p.m. NNN. After 87 weeks, the experiment was terminated and the esophageal tumors were counted. Rats that were given untreated drinking water developed no tumors. Rats that were given 5 p.p.m. NNN and unadulterated AIN-76A diet had an esophageal tumor incidence of 71% and a multiplicity of 1.57 tumors/animal. The two dietary concentrations of PPITC reduced the incidence and multiplicity of NNN-induced esophageal tumors by >95%. These results demonstrate the remarkable chemopreventive efficacy of PPITC in the NNN-induced esophageal tumor model.
Insights
Dietary 3-phenylpropyl isothiocyanate (PPITC) significantly inhibited esophageal N-nitrosonornicotine (NNN) metabolism and reduced NNN-induced esophageal tumors by over 95% in rats, demonstrating its chemopreventive potential.
Area of Science:
- Chemoprevention
- Gastrointestinal Oncology
- Dietary Compounds
Background:
- N-nitrosonornicotine (NNN) is a potent esophageal carcinogen.
- Dietary isothiocyanates are known for their potential anti-cancer properties.
- Understanding the metabolism of NNN is crucial for developing chemopreventive strategies.
Purpose of the Study:
- To investigate the inhibitory effects of various dietary isothiocyanates on esophageal NNN metabolism.
- To evaluate the chemopreventive efficacy of 3-phenylpropyl isothiocyanate (PPITC) against NNN-induced esophageal tumorigenesis.
Main Methods:
- Rats were fed diets containing different isothiocyanates (BITC, PEITC, PPITC, PBITC) for two weeks.
- Esophageal tissues were incubated with [5-3H]NNN in vitro to measure NNN metabolite production.
- Rats were administered NNN in drinking water and fed diets with varying concentrations of PPITC to assess tumor development over 87 weeks.
Main Results:
- Dietary PPITC demonstrated the most significant inhibition of NNN metabolism (55-91%).
- PPITC administration markedly reduced NNN-induced esophageal tumor incidence and multiplicity by over 95% compared to controls.
- No tumors were observed in rats not exposed to NNN.
Conclusions:
- 3-phenylpropyl isothiocyanate (PPITC) effectively inhibits esophageal NNN metabolism.
- PPITC exhibits remarkable chemopreventive efficacy against NNN-induced esophageal tumors in a rat model.
- PPITC is a promising agent for the prevention of esophageal cancer.