Featured Research

from universities, journals, and other organizations

Synthetic Molecule Makes Cancer Cells Commit Suicide

Date:
November 13, 2007
Source:
Howard Hughes Medical Institute
Summary:
Researchers have developed a small molecule that can turn the survival signal for a variety of cancer cells into a death signal. The molecule mimics the activity of Smac, a protein that triggers the suicide of some types of cancer cells. The findings suggest that Smac-mimetic compounds could be useful as targeted cancer treatments for lung and other cancers.

Triggering cancer cells' own suicide bomb.
Credit: Illustration by Sean Petersen, Courtesy of Howard Hughes Medical Institute

Howard Hughes Medical Institute researchers have developed a small molecule that can turn the survival signal for a variety of cancer cells into a death signal. The molecule mimics the activity of Smac, a protein that triggers the suicide of some types of cancer cells.

The researchers say their findings suggest that Smac-mimetic compounds could be useful as targeted cancer treatments for lung and other cancers. Such therapy may be less toxic to healthy cells than current compounds used in cancer chemotherapy.

The researchers, led by Howard Hughes Medical Institute investigator Xiaodong Wang, published their findings in the November, 2007, issue of the journal Cancer Cell. Wang is at the University of Texas Southwestern Medical Center.

Cells that are defective or that become unnecessary during growth and development are induced to commit suicide through a finely balanced process known as apoptosis, or programmed cell death. A protein called Smac, which is a shortened version of "second mitochondria-derived activator of apoptosis," is a part of the cell's programmed cell death machinery. When that machinery is switched on, Smac is released from the mitochondria and triggers the pathway that kills damaged or abnormal cells. Cancer cells, however, can survive Smac's death signal by switching off the apoptotic machinery.

To see if they could get around this problem, Wang and other researchers have developed small-molecule mimetics of Smac that can enter the cell and trigger apoptosis. These mimetic molecules do their damage without the need for the Smac signal from the mitochondria. In earlier studies, Wang and his colleagues found that a Smac mimetic that they developed in the lab could kill cancer cells in culture. But they found that the cancer cells are only killed when the mimetic molecule is introduced in conjunction with another component of the apoptotic machinery known as TNFá.

In the new studies published in Cancer Cell, Wang and his colleagues found that a significant percentage of human non-small-cell lung cancer cell lines were sensitive to treatment by the Smac mimetic alone. When the researchers introduced those sensitive cells into mice and allowed them to produce tumors, they found that the Smac mimetic caused the tumors to regress and, in some cases, even disappear.

"These findings made us wonder what it was about these cell lines that made them sensitive to the Smac mimetic alone," said Wang. "Cancer cells are hard to kill, but these cell lines seemed to have already become sensitized to apoptosis."

The researchers' studies revealed that the sensitive cell lines produced their own TNFá, so they were already "primed" for apoptosis. The paradox, said Wang, is that TNFá signaling is also part of a complex pathway that gives cancer cells a "survival" signal, offering them a growth advantage. The researchers also found that some breast cancer and melanoma cell lines were sensitive to the Smac mimetic alone.

"Thus, in these cancer cell lines, the TNFá survival advantage turns out to be a fatal flaw, because the same pathway can be switched to apoptosis by Smac mimetics," said Wang. "So, for some cancers, we might be able to use Smac mimetics as a single treatment agent. And we can use the presence of TNFá as a marker to tell us which tumors will respond to the Smac mimetic alone."

"People have been suspecting for a long time that some cancer cells may somehow turn on their apoptotic pathway already," said Wang. "And now we know what pathway they turn on and why. We can take advantage of this phenomenon for potential cancer therapy by switching a signal into a deadly one with Smac mimetics."


Story Source:

The above story is based on materials provided by Howard Hughes Medical Institute. Note: Materials may be edited for content and length.


Cite This Page:

Howard Hughes Medical Institute. "Synthetic Molecule Makes Cancer Cells Commit Suicide." ScienceDaily. ScienceDaily, 13 November 2007. <www.sciencedaily.com/releases/2007/11/071112133819.htm>.
Howard Hughes Medical Institute. (2007, November 13). Synthetic Molecule Makes Cancer Cells Commit Suicide. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2007/11/071112133819.htm
Howard Hughes Medical Institute. "Synthetic Molecule Makes Cancer Cells Commit Suicide." ScienceDaily. www.sciencedaily.com/releases/2007/11/071112133819.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) — Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) — The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) — Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) — New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
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:
from the past week

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