Related Experiment Video
Updated: Dec 12, 2025
Application of AlDeSense to Stratify Ovarian Cancer Cells Based on Aldehyde Dehydrogenase 1A1 Activity
Published on: March 31, 2023
Allicin, a Potent New Ornithine Decarboxylase Inhibitor in Neuroblastoma Cells
Chad R Schultz1, Martin C H Gruhlke2, Alan J Slusarenko2
1Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, Michigan 49503, United States.
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.
Insights
Allicin, a compound from garlic, potently inhibits ornithine decarboxylase (ODC), an enzyme crucial for neuroblastoma cell growth. This natural product shows promise as a novel anticancer agent, potentially enhancing other treatments.
Area of Science:
- Biochemistry
- Oncology
- Natural Products Chemistry
Background:
- Neuroblastoma (NB) is a pediatric cancer driven by c-MYC/MYCN, which upregulate Ornithine Decarboxylase (ODC).
- ODC synthesizes polyamines, which are oncometabolites promoting NB cell proliferation.
- ODC is a validated anticancer target, making its inhibitors valuable therapeutic candidates.
Purpose of the Study:
- To investigate allicin, a reactive sulfur species from garlic (Allium sativum L.), as a potential inhibitor of Ornithine Decarboxylase (ODC).
- To evaluate allicin's efficacy in inhibiting ODC activity and its downstream effects on neuroblastoma cell proliferation and survival.
Main Methods:
- In vitro radioactive assay using purified human ODC to determine allicin's inhibitory potency (IC50).
- Assessment of allicin's effect on ODC enzyme activity in actively proliferating human NB cells.
- Measurement of cellular polyamine levels, cell proliferation (IC50), and induction of apoptosis in NB cells treated with allicin.
Main Results:
- Allicin demonstrated potent inhibition of human ODC in vitro (IC50 = 11 nM), significantly outperforming DFMO (IC50 = 252 μM).
- Allicin reversibly S-thioallylates cysteines in the ODC homodimer.
- In NB cells, allicin inhibited ODC activity, reduced polyamine levels, suppressed proliferation (IC50 = 9-19 μM), and induced apoptosis.
Conclusions:
- Allicin is identified as a novel and potent inhibitor of Ornithine Decarboxylase (ODC).
- Allicin exhibits significant anticancer effects against neuroblastoma cells by targeting ODC and polyamine biosynthesis.
- Allicin holds potential for development as a therapeutic agent, possibly in combination with existing anticancer treatments to enhance efficacy and reduce side effects.
Related Concept Videos
01:19Allosteric Proteins-ATCase
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
02:34Inhibition of Cdk Activity