Featured Research

from universities, journals, and other organizations

Scientists create new process to 'program' cancer cell death

Date:
September 8, 2010
Source:
California Institute of Technology
Summary:
Researchers have engineered a fundamentally new approach to killing cancer cells. The process uses small RNA molecules that can be programmed to attack only specific cancer cells; then, by changing shape, those molecules cause the cancer cells to self-destruct.

In lab-grown human brain, prostate, and bone cancer cells, small conditional RNAs (light and dark blue) bind to a targeted RNA cancer mutation (orange and green), triggering self-assembly of a long double-stranded RNA polymer that activates an innate immune response (gray turns to red) leading to cell death. No measurable reduction in numbers is observed for cells lacking targeted cancer mutations.
Credit: Suvir Venkataraman, William M. Clemons, Jr., Niles A. Pierce/Caltech

Researchers at the California Institute of Technology (Caltech) have engineered a fundamentally new approach to killing cancer cells. The process -- developed by Niles Pierce, associate professor of applied and computational mathematics and bioengineering at Caltech, and his colleagues -- uses small RNA molecules that can be programmed to attack only specific cancer cells; then, by changing shape, those molecules cause the cancer cells to self-destruct.

Related Articles


In conventional chemotherapy treatments for cancer, patients are given drugs that target cell behaviors typical of -- but not exclusive to -- cancer cells. For example, cancer drugs commonly attack cells that divide rapidly, because such accelerated division is a hallmark of most cancer cells. Unfortunately, rapid cell division is a property of normal cells in the bone marrow, digestive tract, and hair follicles, and so these cells are also killed, leading to a host of debilitating side effects.

A better method, says Pierce, is to create drugs that can first distinguish cancer cells from healthy cells and then, once those cells have been spotted, mark them for destruction; in other words, to produce molecules that diagnose cancer cells before eradicating them. This type of therapy could do away with the side effects associated with conventional chemotherapy treatments. It also could be tailored on a molecular level to individual cancers, making it uniquely specific.

In a paper slated to appear in the Proceedings of the National Academy of Sciences (PNAS), Pierce and his colleagues describe just such a process. It employs hairpin-shaped molecules known as small conditional RNAs, which are less than 30 base pairs in length. (An average gene is thousands of base pairs long.)

The researchers' method involves the use of two different varieties of small conditional RNA. One is designed to be complementary to, and thus to bind to, an RNA sequence unique to a particular cancer cell -- say, the cells of a glioblastoma, an aggressive brain tumor. In order to bind to that cancer mutation, the RNA hairpin must open -- changing the molecule from one form into another -- which, in turn, exposes a sequence that can spontaneously bind to the second type of RNA hairpin. The opening of the second hairpin then reveals a sequence that binds to the first type of hairpin, and so on.

In this way, detection of the RNA cancer marker triggers the self-assembly of a long double-stranded RNA polymer. As part of an innate antiviral immune response, human cells defend against infection using a protein called protein kinase R (PKR) to search for long double-stranded viral RNA, which should not be present in healthy human cells. If PKR indeed detects long double-stranded RNA within a cell, the protein triggers a cell-death pathway to eliminate the cell. "The small conditional RNAs trick cancer cells into self-destructing by selectively forming long double-stranded RNA polymers that mimic viral RNA," says Pierce. "There is, however, no virus."

Pierce and his colleagues tested the process on lab-grown human cells derived from three types of cancers: glioblastoma, prostate carcinoma, and Ewing's sarcoma (a type of bone tumor). "We used three different pairs of small conditional RNAs," with each pair designed to recognize a marker found in one of the three types of cancer, he explains. "The molecules caused a 20- to 100-fold drop in the numbers of cancer cells containing the targeted RNA cancer markers, but no measurable reduction in cells lacking the markers." For example, he explains, "drug 1 killed cancer 1 but not cancers 2 and 3, while drug 2 killed cancer 2 but not cancers 1 and 3, and drug 3 killed cancer 3 but not cancers 1 and 2."

"Conceptually," Pierce says, "small conditional RNAs provide a versatile framework for diagnosing and treating disease one cell at a time within the human body. However," he notes, "many years of work remain to establish whether the conceptual promise of small conditional RNAs can be realized in human patients."

The other coauthors of the paper, "Selective cell death mediated by small conditional RNAs," are Caltech research scientist Suvir Venkataraman and former Caltech graduate students Robert M. Dirks and Christine T. Ueda. The work was funded by the National Cancer Institute, the Elsa U. Pardee Foundation, the National Science Foundation's Molecular Programming Project, the Caltech Center for Biological Circuit Design, the Caltech Innovation Initiative, the Beckman Institute at Caltech, and a Caltech grubstake fund.


Story Source:

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


Journal Reference:

  1. Suvir Venkataraman, Robert M. Dirks, Christine T. Ueda, Niles A. Pierce. Selective cell death mediated by small conditional RNAs. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1006377107

Cite This Page:

California Institute of Technology. "Scientists create new process to 'program' cancer cell death." ScienceDaily. ScienceDaily, 8 September 2010. <www.sciencedaily.com/releases/2010/09/100907104057.htm>.
California Institute of Technology. (2010, September 8). Scientists create new process to 'program' cancer cell death. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2010/09/100907104057.htm
California Institute of Technology. "Scientists create new process to 'program' cancer cell death." ScienceDaily. www.sciencedaily.com/releases/2010/09/100907104057.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com
WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
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