Cisplatin Hitches A Ride On RNA

The widely used cancer drug cisplatin, Cl₂Pt(NH₃)₂, accumulates up to 20 times more on a cell’s RNA than its DNA, Oregon chemists report (ACS Chem. Biol., DOI: 10.1021/cb200279p). For decades, scientists have thought that cisplatin kills cancer cells by latching onto DNA and gumming up DNA replication and transcription. They didn’t believe cisplatin would build up on RNA because, unlike DNA, RNA turns over rapidly in cells. Victoria J. DeRose and colleagues at the University of Oregon decided to test that assumption. The team treated yeast cell cultures with cisplatin and then isolated nucleic acids from the dying cells for mass spectrometry measurements. On a per-nucleotide basis, cisplatin bound to DNA three times more often than to RNA. However, yeast cells contain more RNA than DNA, so between fourfold and 20-fold more cisplatin landed on RNA than DNA, the researchers note, with a majority of the platinum molecules latched onto RNA in the ribosome. DeRose’s team next plans to confirm its results using human cancer cells and study how cisplatin binding changes RNA activity.