A daffodil compound, haemanthamine, could prevent tumor cells resistance to apoptosis and uncontrolled proliferation by inhibiting ribosome function and biogenesis (Structure, CellPress)
Led by Denis Lafontaine (Laboratory of RNA Molecular Biology, Faculty of Sciences, U-CRC), the researchers extracted a natural anti-cancer compound from Daffodil (Amarylidaceae Narcissus). They established that this compound, an alkaloid called haemanthamine, binds to the ribosome - the nanomachine responsible for making proteins. To ensure their growth, cancer cells are dependent on increased protein synthesis: they are therefore particularly sensitive to treatments that inhibit the production and function of ribosomes.
In this new study, researchers have shown that haemanthamine prevents the production of proteins by ribosomes, slowing the growth of cancer cells. Haemanthamine also inhibits the production of ribosomes in the nucleolus (ribosome factory): this nucleolar stress leads to the activation of an anti-tumor pathway leading to the p53 protein stabilization, which leads to the elimination of cancer cells.
This study provides, for the first time, a molecular explanation of the anti-tumor activity of the daffodil, used for centuries in folk medicine. In the near future, Denis Lafontaine's team, in collaboration with Véronique Mathieu (Faculty of Pharmacy, U-CRC) will test the effect on ribosome biogenesis and function of four Amaryllidaceae alkaloids, representing the range of chemical diversity of these compounds. Their goal will be to quickly identify the most promising chemical skeleton for later development in anti-cancer therapy.