Cisplatin surprise: Drug binds quickly to RNA
Recent research has demonstrated that cisplatin binds 20-fold more pervasively to RNA than to DNA, making RNA a potential new drug target for the platinum compound, which is used to fight tumors in nearly 70% of all human cancers.
Cisplatin is used extensively in chemotherapy because it effectively reduces tumor size, but patients often have to discontinue use of the agent due to toxicities including renal insufficiency, tinnitus, anemia, gastrointestinal problems, and nerve damage. Known to bind to DNA, cisplatin was thought to attach to RNA only fleetingly, according to Victoria J. DeRose, a chemist at University of Oregon in Eugene and coauthor of the ACS Chemical Biology paper detailing her group's cisplatin/RNA revelation.
“We're looking at RNA as a new drug target,” affirmed DeRose in a statement announcing the findings. “We think this is an important discovery because we know that RNA is very different in tumors than it is in regular healthy cells.”
The investigators applied cisplatin to rapidly dividing and RNA-rich yeast cells known as Saccharomyces cerevisiae. While they did expect the platinum to bind to RNA, they thought the RNA would degrade and the drug would be shunted out of the cell. Instead, they found that the RNA retained the platinum, and that the platinum attached to the RNA quickly—like glue, to specific sections—appearing on the RNA as quickly as 1 hour after treatment. Although the platinum was 2 to 3 times denser on DNA, there was a much higher whole-cell concentration on RNA.
The new information may eventually help scientists find ways to target cisplatin toward specific sections of RNA and thus reduce the drug's toxicity.