Abstract
The natural product allicin is a reactive sulfur species (RSS) from garlic (Allium sativum L.). 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 vitro assay using purified human ODC. Allicin was ∼23 000-fold more potent (IC50 = 11 nM) than DFMO (IC50 = 252 μM), under identical in vitro assay 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 (IC50 9-19 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.
Full text
