Allicin, a Potent New Ornithine Decarboxylase Inhibitor in Neuroblastoma Cells

• Published in: Journal of natural products (Washington, D.C.) Vol. 83; no. 8; pp. 2518 - 2527
• Main Authors: Schultz, Chad R, Gruhlke, Martin C. H, Slusarenko, Alan J, Bachmann, André S
• Format: Journal Article
• Language: English
• Published: American Chemical Society and American Society of Pharmacognosy 28-08-2020
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.0c00613

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.