Navigation Links
Cancer drug cisplatin found to bind like glue in cellular RNA
Date:11/21/2011

EUGENE, Ore. -- (Nov. 21, 2011) -- 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.


'/>"/>

Contact: Jim Barlow
jebarlow@uoregon.edu
541-346-3481
University of Oregon
Source:Eurekalert  

Related medicine news :

1. New breast cancer screening guidelines released
2. BRAF addiction of thyroid cancers makes them therapeutically vulnerable
3. IBD patients face increased skin cancer risk
4. FDA Revokes Approval of Avastin for Breast Cancer
5. Colon cancer screening campaign erases racial, gender gaps in use of colonoscopy
6. Tender Breasts From Combo HRT Linked to Higher Cancer Risk
7. Combo hormone therapy has increased breast cancer risk over estrogen alone
8. PBX1 identified as a new pioneer factor underlying progression in breast cancer
9. Cancer Doctors Still Not Great With Patients Pain
10. Early breast cancer detection saves lives
11. New device uses gold nanoparticles to test for lung cancer
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Cancer drug cisplatin found to bind like glue in cellular RNA
(Date:3/30/2017)... ... March 30, 2017 , ... ... the eve of Autism Awareness Month, representatives from Organic Consumers Association, National Health ... Focus For Health Foundation, A Voice for Choice, Moms Across America, Freedom and ...
(Date:3/30/2017)... ... March 30, 2017 , ... This morning, more than 275 ... their support for an independent Vaccine Safety Commission. Five of the signers of ... will hold a press conference at 9:00 AM Friday, March 31 at ...
(Date:3/29/2017)... ... March 29, 2017 , ... The Professional Squash ... has enlisted New York City-based sports and entertainment marketing firm Leverage Agency as ... opportunities for the Professional Squash Association (PSA), which includes first-time ever title sponsorship, ...
(Date:3/29/2017)... ... ... Youth Futures International (YFI) premiered its Serve, Learn, & Empower program in ... who have participated in the program every summer. The 2017 Serve, Learn, & ... enrollment. Visit http://www.ghana.yfiexperience.org to learn more. , “I have sent my ...
(Date:3/29/2017)... Louisiana (PRWEB) , ... March 29, 2017 , ... ... in three Hours at a Walgreens store in Mississippi. AngioGenesis Labs, makers of ... Walgreens Stores in two southeastern states. Ingredients in HeartBoost, an over the counter ...
Breaking Medicine News(10 mins):
(Date:3/29/2017)... 29, 2017  Maxor National Pharmacy Services, LLC ("Maxor"), ... has named Leah Bailey as General Counsel.  Bailey ... the company. With more than 13 years ... years focused on health care, Bailey joins the Maxor ... Prime, Bailey advised the PBM, Specialty, and Mail Order ...
(Date:3/29/2017)... -- The Pharmaceutical Care Management Association (PCMA) today released the ... out-of-pocket spending: According to ... average amount spent out-of-pocket for drugs continues to decline, ... down from 23% in 2006. Rising ... problem. Health plans don,t have unlimited funds to pay ...
(Date:3/29/2017)... Research and Markets has announced the addition of the "Ablation ... offering. ... ablation device global market is expected to grow at high single ... Ablation is the minimally invasive therapeutic tissue excision procedure used for ... to the removal of abnormally conducting cardiac tissue in atrial fibrillation ...
Breaking Medicine Technology: