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The natural product allicin is a reactive sulfur species (RSS) from garlic (Allium sativumL.). Neuroblastoma (NB) is an early childhood cancer arising from the developing peripheral nervous system. Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the biosynthesis of polyamines, which are oncometabolites that contribute to cell proliferation in NB and other c-MYC/MYCN-driven cancers. Both c-MYC and MYCN directly transactivate the E-box gene ODC1, a validated anticancer drug target. We identified allicin as a potent ODC inhibitor in a specific radioactive in vitroassay using purified human ODC. Allicin was ∼23 000-fold more potent (IC50= 11 nM) than DFMO (IC50= 252 μM), under identical in vitroassay conditions. ODC is a homodimer with 12 cysteines per monomer, and allicin reversibly S-thioallylates cysteines. In actively proliferating human NB cells allicin inhibited ODC enzyme activity, reduced cellular polyamine levels, inhibited cell proliferation (IC509–19 μM), and induced apoptosis. The natural product allicin is a new ODC inhibitor and could be developed for use in conjunction with other anticancer treatments, the latter perhaps at a lower than usual dosage, to achieve drug synergism with good prognosis and reduced adverse effects.

The multiplicity of chemical structures of sulfur containing compounds, influenced in part by the element's several oxidation states, directly results in diverse modes of action for sulfur-containing natural products synthesized as secondary metabolites in plants. Sulfur-containing natural products constitute a formidable wall of defence against a wide range of pathogens and pests. Steady progress in the development of new technologies have advanced research in this area, helping to uncover the role of such important plant defence molecules like endogenously-released elemental sulphur, but also deepening current understanding of other better-studied compounds like the glucosinolates. As studies continue in this area, it is becoming increasingly evident that sulfur and sulfur compounds play far more important roles in plant defence than perhaps previously suspected.