Identification of the Anti-cancer Protein Targets of the Garlic Compound Ajoene
Dr Catherine Kaschula
Title of the project
Identification of the anti-cancer protein targets of the garlic compound ajoene.
Cancer is a hyper-proliferative disease which results in over six million deaths per year. Most malignancies are diagnosed and treated at advanced stages with poor overall survival, thus cancer prevention is a key opportunity for managing the pandemic. Several lines of evidence indicate that 50 – 80% of cancers are preventable as their causation is largely exogenous with diet and lifestyle playing an important role.
Garlic is a dietary medicinal plant that has been used for centuries both as a flavour enhancer and for its beneficial health effects. Crushed cloves are rich in sulfur containing compounds collectively termed garlic organosulfur compounds (OSCs) that include the compound ajoene. Garlic is well documented to have cancer preventative properties based on epidemiological studies which is largely attributed to the presence of the OSCs.
Garlic OSCs have been shown to inhibit cancer cell proliferation and induce apoptosis at micromolar concentrations in cancer cells. We have previously shown that ajoene is a natural non-steroidal anti-inflammatory drug (NSAID) able to inhibit the Cox-2 enzyme activity which may partly explain its cancer preventative properties. NSAIDs favourably dampen the pro-inflammatory response in cancer to aid in tumour control.
On a chemical level, we have previously shown that garlic OSCs are able to S-thiolate susceptible cysteine residues on target proteins in immune and cancer cells which is responsible for some of their biological effects. In the current project we would like to identify the protein targets of the garlic compound ajoene in cancer cells. We will determine whether ajoene targets these proteins in tumours by studying whether it is able to biotinylate these proteins in the tumour and whether it is able to inhibit tumour growth.