Featured Research

from universities, journals, and other organizations

Novel drug action against solid tumors explained

Date:
August 11, 2014
Source:
UC Davis Comprehensive Cancer Center
Summary:
Researchers have discovered how a drug that deprives the cells of a key amino acid specifically kills cancer cells. The study describes how arginine starvation specifically kills tumor cells by a novel mechanism involving mitochondria dysfunction, reactive oxygen species generation, nuclear DNA leakage and chromatin autophagy, where leaked DNA is captured and "eaten" by giant autophagosomes.

Researchers at UC Davis, City of Hope, Taipai Medical University and National Health Research Institutes in Taiwan have discovered how a drug that deprives the cells of a key amino acid specifically kills cancer cells.

Related Articles


Their paper, published in Proceedings of the National Academy of Sciences, is the culmination of nearly a decade of research into the role of arginine -- and its deprivation -- in the generation of excessive autophagy, a process in which the cell dies by eating itself.

Study co-author Hsing-Jien Kung, a cancer biologist and UC Davis professor emeritus who now leads the National Health Research Institutes in Taipei, Taiwan, first discovered the mechanism by which arginine deprivation works in 2009, when he led basic science research at the UC Davis Comprehensive Cancer Center.

"Traditional cancer therapies involve 'poisoning' by toxic chemicals or 'burning' by radiation cancer cells to death, which often have side effects," Kung said. "An emerging strategy is to 'starve' cancer cells to death, taking advantage of the different metabolic requirements of normal and cancer cells. This approach is generally milder, but as this study illustrates, it also utilizes a different death mechanism, which may complement the killing effects of the conventional therapy."

The discovery led to the further development of a drug now being tested in several clinical trials against melanoma, prostate, liver, sarcoma and other cancers that lack an enzyme that helps synthesize arginine, an amino acid with an essential role in cell division, immune function and hormone regulation.

The study published today describes how arginine starvation specifically kills tumor cells by a novel mechanism involving mitochondria dysfunction, reactive oxygen species generation, nuclear DNA leakage and chromatin autophagy, where leaked DNA is captured and "eaten" by giant autophagosomes.

Unlike apoptosis, a cell-death process in which the DNA is damaged within the cell nucleus, in chromatin-autophagy the nucleus is fragmented and its pieces shuttled off to the lysosome (an organelle within the cell membrane) where the fragments are degraded.

"It has long been recognized that some cancer cells are resistant to apoptosis," said Richard Bold, professor and chief of surgical oncology at the UC Davis Comprehensive Cancer and a co-author of the study. "Now, we have another way to induce cells to undergo death that overcomes resistance to traditional apoptosis associated with cancer."

The authors suggest that using arginine-deprivation induced autophagy may also spare patients the toxicity associated with chemotherapy alone.

The drug examined in the study is ADI-PEG20, developed by Polaris Pharmaceuticals of San Diego. ADI-PEG20 is an enzyme that degrades arginine, which normally would be available to the cell, breaking it down into its precursors. The agent is currently in phase III clinical trials in liver cancer, phase II in melanoma and phase I in prostate cancer.

Primo Lara, UC Davis oncologist and associate director of translational research at the cancer center, led a phase I study of the drug in patients with advanced lung, prostate and oral cancers. He reported that combined with a chemotherapy agent, the drug was feasible and reasonably tolerated. He is currently recruiting advanced prostate cancer patients for a new phase I trial of the drug combination.

"This opens up a new field," said Bold. "Now we search for other agents that use this method and translate those into clinical trials."


Story Source:

The above story is based on materials provided by UC Davis Comprehensive Cancer Center. Note: Materials may be edited for content and length.


Cite This Page:

UC Davis Comprehensive Cancer Center. "Novel drug action against solid tumors explained." ScienceDaily. ScienceDaily, 11 August 2014. <www.sciencedaily.com/releases/2014/08/140811151123.htm>.
UC Davis Comprehensive Cancer Center. (2014, August 11). Novel drug action against solid tumors explained. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2014/08/140811151123.htm
UC Davis Comprehensive Cancer Center. "Novel drug action against solid tumors explained." ScienceDaily. www.sciencedaily.com/releases/2014/08/140811151123.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
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