C. Kaschula - The chemistry of garlic and its ability to kill cancer cells.
Channel: Icgeb
Date: 2021-09-08

Cancer is a disease that affects people regardless of race, geography or socioeconomic status. With limited and often expensive treatment options, prevention is an attractive intervention strategy against the disease. It is well known that many cancers are largely preventable with diet and lifestyle playing a major role. In this context, garlic is a medicinal and dietary plant
that has been used in folk medicine for centuries, and it is active against many different stages of cancer. The bioactive compounds in garlic are produced during the processing of the cloves, and one of these compounds is the vinyl disulfide organosulfur compound ajoene which we have been studying for many years. Ajoene acts by S-thiolating cysteine residues on proteins, akin to a post-translational modification, resulting in a number of downstream effects. We have developed a synthetic route to ajoene analogues which has enabled us to synthesise more potent ajoenes, as well as fluorescent and biotinylated analogues. By tracking the movement of fluorescent ajoene, we found that it localises to the endoplasmic reticulum
of cancer cells where it interferes with protein folding and activates the unfolded protein response. In another study, we used a biotinylated ajoene to tag and pull down the ajoene protein targets. Many of these targets contain known reactive cysteines which are involved in the maintenance of cancer homeostasis. Our studies provide some mechanistic evidence into the anti-cancer activity of this remarkable, and accessible natural product.