Effects of supplemented methionine on the efficacy of platinum drugs in the yeast model organism

Platinum (Pt) drugs are used in half of all anticancer treatments. A common way to study Pt drugs is by using S. cerevisiae (brewer’s yeast) as a model cellular organism. One of the most commonly used strains of yeast is BY4741, which is auxotrophic for several small-molecule nutrients, including some amino acids and the base uracil. Therefore, these must be supplemented in the cell culture medium. One of the amino acids is methionine, which is known to be able to bind and even chelate heavy metals. Methionine-supplemented media continues to be used to study Pt drugs in yeast, especially BY4741, yet the potential for methionine to interfere with the activity of Pt drugs appears to be a possibility in some studies. We have investigated the toxicity of the Pt drug cisplatin in such systems and shown that methionine supplementation of the culture media affects the measured toxicity (IC50) of cisplatin and may potentially affect the uptake or localization of the drug. We have also shown that methionine inhibits the binding of Pt to model DNA in vitro. A more complete understanding of the Pt–yeast model system will clarify its use with this important class of anticancer drug.