Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer drug cisplatin found to bind like glue in cellular RNA

22.11.2011
Discovery opens a new targeting scheme for drug delivery that potentially would reduce toxic side effects

An anti-cancer drug used extensively in chemotherapy binds pervasively to RNA -- up to 20-fold more than it does to DNA, a surprise finding that suggests new targeting approaches might be useful, according to University of Oregon researchers.

Medical researchers have long known that cisplatin, a platinum compound used to fight tumors in nearly 70 percent of all human cancers, attaches to DNA. Its attachment to RNA had been assumed to be a fleeting thing, says UO chemist Victoria J. DeRose, who decided to take a closer look due to recent discoveries of critical RNA-based cell processes.

"We're looking at RNA as a new drug target," she said. "We think this is an important discovery because we know that RNA is very different in tumors than it is in regular healthy cells. We thought that the platinum would bind to RNA, but that the RNA would just degrade and the platinum would be shunted out of the cell. In fact, we found that the platinum was retained on the RNA and also bound quickly, being found on the RNA as fast as one hour after treatment."

The National Institutes of Health-supported research is detailed in a paper placed online ahead of regular publication in ACS Chemical Biology, a journal of the American Chemical Society. Co-authors with DeRose, a member of the UO chemistry department and Institute of Molecular Biology, were UO doctoral students Alethia A. Hostetter and Maire F. Osborn.

The researchers applied cisplatin to rapidly dividing and RNA-rich yeast cells (Saccharomyces cerevisiae, a much-used eukaryotic model organism in biology). They then extracted the DNA and RNA from the treated cells and studied the density of platinum per nucleotide with mass spectrometry. Specific locations of the metal ions were further hunted down with detailed sequencing methods. They found that the platinum was two to three times denser on DNA but that there was a much higher whole-cell concentration on RNA. Moreover, the drug bound like glue to specific sections of RNA.

DeRose is now pursuing the ramifications of the findings. "Can this drug be made to be more or less reactive to specific RNAs?" she said. "Might we be able to go after these new targets and thereby reduce the drug's toxicity?"

While cisplatin is effective in reducing tumor size, its use often is halted because of toxicity issues, including renal insufficiency, tinnitus, anemia, gastrointestinal problems and nerve damage.

The extensive roles of RNA have come under intense scrutiny since completion of the human genome opened new windows on DNA, life's building blocks. It had been assumed that RNA was simply a messenger that coded for protein activity. New technologies, DeRose said, have shown that a vast amount of RNA performs an amazing level of different functions in gene expression, controlling it in specific ways during development or disease, particularly in cancer cells.

In this project, DeRose's team only explored cisplatin's binding on two forms of RNA: ribosomes, where the highest concentration of the drug was found; and messenger RNA. There are more areas to be looked at, said DeRose, whose group initially developed experience using and mapping platinum's activity as a mimic for other metals in her research on RNA enzymes.

DeRose is now planning work with UO colleague Hui Zong, a biologist studying how cancer emerges, to extend the research into mouse cells to see if the findings in yeast RNA hold up. An additional collaboration with UO chemist Michael Haley involves the creation of new platinum-based drugs with "reaction handles" that will allow researchers to easily pull the experimental drugs out of cells, while still attached to their biological targets. New developments in 'deep' RNA sequencing, available through the UO's Genomic Core Facilities, could then provide a much broader view of platinum's preferred resting sites in the cell.

About the University of Oregon

The University of Oregon is among the 108 institutions chosen from 4,633 U.S. universities for top-tier designation of "Very High Research Activity" in the 2010 Carnegie Classification of Institutions of Higher Education. The UO also is one of two Pacific Northwest members of the Association of American Universities.

Source: Victoria DeRose, professor of chemistry, 541-346-3568, derose@uoregon.edu

Links:

DeRose chemistry faculty page:
http://www.uoregon.edu/~chem/fac.html?derose
DeRose at Institute of Molecular Biology:
http://molbio.uoregon.edu/facres/derose.html
Department of Chemistry:
http://chemistry.uoregon.edu/

Jim Barlow | EurekAlert!
Further information:
http://www.uoregon.edu

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>