Mechanisms by Which Garlic and Allyl Sulfur Compounds Suppress Cancer
J. A. Milner
Nutritional Science Research Group, Division Cancer Prevention, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Rockville, MD 20892.
Garlic [Allium sativum] is among the oldest of all cultivated plants.
Throughout history it has been revered for its medicinal properties
with benefits proposed to encompass antimicrobial, antithrombotic,
hypolipidemic, antiarthritic, hypoglycemic and antitumor effects. In
some parts of the world the sales of garlic preparations ranks with
those of leading prescription drugs. A variety of epidemiological and
preclinical studies support the ability of allium foods, particularly
garlic, to retard the cancer process. While epidemiological evidence
suggests allium foods may retard the risk of cancer at several sites
the strongest evidence exists for the gastrointestinal tract. It is
unclear if the variability in epidemiological observations relates to
the quantity, duration or to the type of garlic preparation provided or
maybe to a modified response resulting from interactions with a host of
dietary or environmental factors or with the consumers genetic
(nutrigenetic) profile. Nevertheless, a recent report suggest that reduced risk of
prostate cancer that was associated with enhanced allium vegetables
consumption was independent of body size, intake of other foods, and
total calorie intake. Fresh garlic extracts, deodorized garlic
preparations, garlic oil and a number of individual organosulfur
compounds derived from garlic have been found to modify one or more
aspects of the cancer process in model systems. While the
mechanism(s) by which garlic and its organosulfur constituents brings
about these effects remains elusive several mechanisms are plausible.
Among the possible mechanisms are alterations in drug metabolizing
enzymes, reduced oxidative damage, suppressed tumor proliferation,
enhanced apoptosis and suppressed angiogenesis. The shifts in
carcinogen metabolism are frequently accompanied by a reduction in the
activity of some cytochrome P450s enzymes, an increase in the activity
of glutathione S-transferases carcinogens and an accompanying reduction in DNA adducts in several target tissues.
Carcinogen induction studies reveal that the benefits of garlic are not
limited to a specific species, to a particular tissue, or to a specific
type of carcinogen. The antiproliferative activity associated with
garlic and related organosulfur compounds has been observed in several
tumor cell lines and may relate to changes in cell cycle regulation
resulting from a reduction in p34(cdc2) kinase activity as a result of
posttranslational changes in phosphorylation. The nutrigenomics
effects of selected allyl sulfur compounds are evident by the
widespread effects on the expressions of genes involved with various
cancer processes. Biochemical analysis of tumors revealed several
characteristic features of apoptosis, including the formation of DNA
ladders, compaction of nuclear DNA, and the activation of caspase-3.
Recently diallyl sulfide (DAS), an organosulfur compound present in
garlic was reported to inhibit angiogenesis in tumor bearing mice. The exact molecular target for any
of the alteration in the cancer process remains to be determined.
Transgenic and knockout models may offer special insights into the
sites of action of garlic and its allyl sulfur components. Overall,
while compelling preclinical evidence supports garlic and its organic
allyl sulfur components are effective inhibitors of the cancer process,
considerably more controlled intervention studies in humans are needed
to truly define who will benefit from garlic and its components and
under what circumstances.
Key words:
garlic, allyl sulfur, tumor, nutrigenomic, diet
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