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Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms
1Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Abstract:
Organic isothiocyanates block the production of tumors induced in rodents by diverse carcinogens (polycyclic aromatic hydrocarbons, azo dyes, ethionine, N-2-fluorenylacetamide, and nitrosamines). Protection is afforded by alpha-naphthyl-, beta-naphthyl-, phenyl-, benzyl-, phenethyl-, and other arylalkyl isothiocyanates against tumor development in liver, lung, mammary gland, forestomach, and esophagus. Many isothiocyanates and their glucosinolate precursors (beta-thioglucoside, N-hydroxysulfate) occur naturally and sometimes abundantly in plants consumed by humans, e.g., cruciferous vegetables. Nevertheless, the possible contributions of isothiocyanates and glucosinolates to the well recognized protective effects against cancer of high consumptions of vegetables are unclear. The anticarcinogenic effects of isothiocyanates appear to be mediated by tandem and cooperating mechanisms: (a) suppression of carcinogen activation by cytochromes P-450, probably by a combination of down-regulation of enzyme levels and direct inhibition of their catalytic activities, which thereby lower the levels of ultimate carcinogens formed; and (b) induction of Phase 2 enzymes such as glutathione transferases and NAD(P)H: quinone reductase, which detoxify any residual electrophilic metabolites generated by Phase 1 enzymes and thereby destroy their ability to damage DNA. Since isothiocyanates block carcinogenesis by dual mechanisms and are already present in substantial quantities in human diets, these agents are ideal candidates for the development of effective chemoprotection of humans against cancer.
Insights
Organic isothiocyanates, found in cruciferous vegetables, effectively block tumor formation in rodents by inhibiting carcinogen activation and boosting detoxification enzymes. These natural compounds show promise for human cancer chemoprevention.
Area of Science:
- Chemoprevention
- Cancer Research
- Molecular Toxicology
Background:
- Organic isothiocyanates are naturally occurring compounds found in cruciferous vegetables.
- These compounds and their precursors (glucosinolates) are consumed by humans.
- The role of isothiocyanates in the cancer-protective effects of vegetable consumption is not fully understood.
Purpose of the Study:
- To investigate the anticarcinogenic mechanisms of organic isothiocyanates.
- To evaluate the potential of isothiocyanates for human cancer chemoprevention.
Main Methods:
- Rodent models were used to study tumor induction by various carcinogens.
- The effects of different arylalkyl isothiocyanates on tumor development were assessed.
- Mechanisms of action, including carcinogen activation and detoxification pathways, were analyzed.
Main Results:
- Organic isothiocyanates demonstrated significant tumor-blocking activity against diverse carcinogens in rodents.
- Protection was observed across multiple organs, including the liver, lung, and esophagus.
- Isothiocyanates suppressed carcinogen activation by inhibiting cytochrome P-450 enzymes.
- They also induced Phase 2 detoxification enzymes, such as glutathione transferases.
Conclusions:
- Isothiocyanates possess dual anticarcinogenic mechanisms: inhibiting carcinogen activation and enhancing detoxification.
- Their presence in human diets and dual action make them promising candidates for cancer chemoprevention strategies.
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