Featured Research

from universities, journals, and other organizations

Chloroquine: Acidic tumor pH inhibits drug effect

Date:
February 11, 2014
Source:
Karolinska Institutet
Summary:
Low pH in tumors counteracts the desired effect of the drug chloroquine, according to a new study. The results might explain possible lack of efficacy of chloroquine in clinical studies.

The results of this study might explain possible lack of efficacy of chloroquine in clinical studies.
Credit: Paola Pellegrini

Low pH in tumors counteracts the desired effect of the drug chloroquine, according to a new study from Karolinska Institutet in Sweden. The results, which are published in the journal Autophagy, might explain possible lack of efficacy of chloroquine in clinical studies.

Related Articles


Chloroquine, a widely used antimalaria drug, is currently under investigation in clinical trials on cancer patients. It is the ability of chloroquine to inhibit autophagy in tumor cells that has piqued researchers' interest. Autophagy is a homeostatic process by which cells eat parts of themselves, so that damaged or unnecessary organelles and toxic proteins are broken down and recycled. In the absence of nutrients, cells resort to autophagy to survive. This way, autophagy helps cancer cells survive in tumor regions that are poor in nutrients and characterised by low oxygen and acidic pH.

Also, tumor cells use autophagy to protect themselves from many forms of anticancer therapies, including chemotherapy. Several studies have shown that inhibition of autophagy often increases chemosensitivity and radiosensitivity in tumor cells. Chloroquine combined with existing cancer treatment is thus considered to be a promising strategy. However, in some cancer models chloroquine seems to be unable to block autophagy, but the underlying mechanisms have not yet been identified.

In the present study, the scientists studied the effect of chloroquine in different cancer cells that were either cultured in acidic pH for a short time or adapted to chronic acidosis. The researchers also studied the effect in tumors grown in mice.

"We discovered that a major consequence of the altered metabolism of tumor cells, the tissue acidification, is responsible for the lack of chloroquine anti-autophagic activity," says Angelo De Milito at the Department of Oncology-Pathology at Karolinska Institutet, principal investigator of the study. "The results suggest that chloroquine might lack efficacy in patients whose tumors are characterized by acidic regions."

In the context of cancer therapy, the finding may be of importance for the translation of preclinical findings to the clinical setting in patients.


Story Source:

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


Journal Reference:

  1. Paola Pellegrini, Angela Strambi, Chiara Zipoli, Maria Hδgg-Olofsson, Maria Buoncervello, Stig Linder, Angelo De Milito. Acidic extracellular pH neutralizes the autophagy-inhibiting activity of chloroquine: Implications for cancer therapies. Autophagy, January 2013 DOI: 10.4161/auto.27901

Cite This Page:

Karolinska Institutet. "Chloroquine: Acidic tumor pH inhibits drug effect." ScienceDaily. ScienceDaily, 11 February 2014. <www.sciencedaily.com/releases/2014/02/140211083816.htm>.
Karolinska Institutet. (2014, February 11). Chloroquine: Acidic tumor pH inhibits drug effect. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2014/02/140211083816.htm
Karolinska Institutet. "Chloroquine: Acidic tumor pH inhibits drug effect." ScienceDaily. www.sciencedaily.com/releases/2014/02/140211083816.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Rural India's Low-Cost Sanitary Pad Revolution

Rural India's Low-Cost Sanitary Pad Revolution

AFP (Nov. 28, 2014) — One man hopes his invention -– a machine that produces cheap sanitary pads –- will help empower Indian women. Duration: 01:51 Video provided by AFP
Powered by NewsLook.com
Research on Bats Could Help Develop Drugs Against Ebola

Research on Bats Could Help Develop Drugs Against Ebola

AFP (Nov. 28, 2014) — In Africa's only biosafety level 4 laboratory, scientists have been carrying out experiments on bats to understand how virus like Ebola are being transmitted, and how some of them resist to it. Duration: 01:18 Video provided by AFP
Powered by NewsLook.com
Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. 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