Featured Research

from universities, journals, and other organizations

Fighting neuroblastomas by blocking DNA replication, repair

Date:
April 16, 2014
Source:
City of Hope
Summary:
PCNA is a protein essential to DNA repair and replication, and researchers are targeting it in neuroblastoma cells in order to halt tumor growth and induce cell death. Neuroblastoma is one of the deadliest childhood cancers, accounting for 15 percent of pediatric cancer deaths. For patients with high-risk neuroblastomas, the five-year survival rate is 40 to 50 percent even with the most rigorous treatments available today.

Neuroblastoma is one of the deadliest childhood cancers, accounting for 15 percent of pediatric cancer deaths. For patients with high-risk neuroblastomas, the five-year survival rate is 40 to 50 percent even with the most rigorous treatments available today.

Related Articles


But those odds may improve soon, thanks to a new compound developed by City of Hope scientists. The compound -- a peptide called R9-caPep -- works by targeting and disrupting proliferating cell nuclear antigens (PCNA), proteins that are essential in DNA synthesis, replication and repair.

The findings were published in PLoS ONE on April 11.

"We have previously reported identifying a subset of PCNAs that are expressed only in cancer cells," said Long Gu, Ph.D., assistant research professor in City of Hope's Department of Molecular and Cellular Biology and first author of the paper. "So we wanted to see if it's possible to single out and inhibit these cancer-associated PCNAs with this peptide, which would mean it's possible to deliver targeted therapy to malignant cells while leaving normal tissues unharmed."

In the study, Gu and his colleagues built R9-caPep to correspond to cancer-associated PCNAs. They then applied it to several neuroblastoma cell cultures. In their observations, they noted that R9-caPep successfully blocked PCNA actions in neuroblastoma cells with much less toxicity in noncancerous cells.

R9-caPep's interference with PCNA in cancer cells led to inhibition of their DNA replication and repair abilities, as well as inducing cell death. R9-caPep also made the neuroblastoma cells more sensitive to cisplatin, a cancer drug that works by damaging DNA.

These findings were further confirmed with animal trials. In this part of the study, Gu's team found that mice who were administered R9-caPep had almost no tumor growth, whereas the tumors in the control groups nearly tripled in volume and approximately doubled in mass over 25 days.

Additionally, the researchers found that R9-caPep was particularly effective on cancer cells with an amplified MYCN gene, which is linked to more aggressive and higher-risk neuroblastomas.

Given these promising findings, Gu and his team are currently conducting further studies to determine how R9-caPep disrupts DNA replication and repair in neuroblastoma cells. They will also be testing this and other peptides' therapeutic potential on breast, lung and pancreatic cancer cells.


Story Source:

The above story is based on materials provided by City of Hope. Note: Materials may be edited for content and length.


Journal Reference:

  1. Long Gu, Shanna Smith, Caroline Li, Robert J. Hickey, Jeremy M. Stark, Gregg B. Fields, Walter H. Lang, John A. Sandoval, Linda H. Malkas. A PCNA-Derived Cell Permeable Peptide Selectively Inhibits Neuroblastoma Cell Growth. PLoS ONE, 2014; 9 (4): e94773 DOI: 10.1371/journal.pone.0094773

Cite This Page:

City of Hope. "Fighting neuroblastomas by blocking DNA replication, repair." ScienceDaily. ScienceDaily, 16 April 2014. <www.sciencedaily.com/releases/2014/04/140416101339.htm>.
City of Hope. (2014, April 16). Fighting neuroblastomas by blocking DNA replication, repair. ScienceDaily. Retrieved March 30, 2015 from www.sciencedaily.com/releases/2014/04/140416101339.htm
City of Hope. "Fighting neuroblastomas by blocking DNA replication, repair." ScienceDaily. www.sciencedaily.com/releases/2014/04/140416101339.htm (accessed March 30, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, March 30, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Soda, Salt and Sugar: The Next Generation of Taxes

Soda, Salt and Sugar: The Next Generation of Taxes

Washington Post (Mar. 30, 2015) — Denisa Livingston, a health advocate for the Dinι Community Advocacy Alliance, and the Post&apos;s Abby Phillip discuss efforts around the country to make unhealthy food choices hurt your wallet as much as your waistline. Video provided by Washington Post
Powered by NewsLook.com
UnitedHealth Buys Catamaran

UnitedHealth Buys Catamaran

Reuters - Business Video Online (Mar. 30, 2015) — The $12.8 billion merger will combine the U.S.&apos; third and fourth largest pharmacy benefit managers. Analysts say smaller PBMs could also merge. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
S. Leone in New Anti-Ebola Lockdown

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015) — Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17 Video provided by AFP
Powered by NewsLook.com
These Popular Antibiotics Can Cause Permanent Nerve Damage

These Popular Antibiotics Can Cause Permanent Nerve Damage

Newsy (Mar. 27, 2015) — A popular class of antibiotic can leave patients in severe pain and even result in permanent nerve damage. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins