Navigation Links
Study: Autophagy predicts which cancer cells live and die when faced with anti-cancer drugs
Date:1/10/2014

When a tumor is treated with an anti-cancer drug, some cells die and, unfortunately, some cells tend to live. A University of Colorado Cancer Center study published in the journal Nature Cell Biology details a possible difference between the susceptible and resistant cells: the rate at which cells are able to cleanse themselves via the process known as autophagy.

"In these studies, say we treat cells with the IC-50 of a drug - at that dose, 50 percent of cells should live and 50 percent of cells should die. But the fundamental question is why does cell A die whereas cell B lives? What we show is that the difference may be due to random variation in the amount of autophagy that's going on," says Andrew Thorburn, PhD, deputy director of the CU Cancer Center.

Previous studies show that autophagy promotes cell survival under conditions of stress or shortage, cells break down non-necessary components to provide energy or use the same strategy to prevent cellular damage by degrading and recycling potentially damaging proteins. And so it seems logical that cancer cells with low autophagy would have high mortality when faced with anti-cancer drugs. However, the current study shows that rates of cell death may increase or decrease depending on levels of autophagy and the specific mechanism of the anti-cancer drug.

"We separated cancer cells into populations with low and high autophagy and then treated them with two drugs, both of which should activate death. Interestingly, when treated with the first drug, cells with high autophagy had the highest mortality. But then when treated with the second drug, cells with low autophagy had the highest mortality. Depending on the drug, the effect of autophagy was opposite," Thorburn says.

Specifically, Thorburn and colleagues including first author Jacob Gump, PhD, treated high- and low-autophagy cell populations with chemicals TRAIL and Fas ligand, which activate cells' death receptors. Cells treated with these chemicals are "told" to die and as the researchers expected, some cells in all populations underwent the programmed cell death known as apoptosis. However, cells with high autophagy were more sensitive to treatment with Fas ligand, whereas cells with low autophagy were more sensitive to TRAIL. Similar differences were seen across types of cancer cells - in some cancers, autophagy protects against these drugs and in others autophagy makes cells more susceptible.

While the work does not necessarily add to our understanding of how autophagy aids cell survival, the group showed how it creates cell death in some tumors when confronted with some drugs: a protein known as FAP-1 is present in some but not all cancer cells where it serves to decrease the ability of Fas ligand to kill the cells. Autophagy degrades this cell-survival protein and this, in turn, makes cells more susceptible to Fas ligand but only in the cells where FAP-1 is normally present.

"If similar variation occurs in other contexts, a cancer cell you're trying to kill could be more or less resistant to whatever you're using to try to kill it depending on its level of autophagy," Thorburn says. Additionally, Thorburn points out that cells in these lab studies tend to be homogenous in their levels of autophagy compared to cells in natural tumor environments. It is likely, he says, these laboratory results will be magnified in actual tumors, where levels of autophagy tend to vary more widely.

While Fas ligand and TRAIL agonists are used in the lab only at this time, Thorburn says the next step in this line of research is to perform similar experiments with drugs that could be used in people.


'/>"/>
Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

Related medicine news :

1. Study: Women not getting enough exercise; at risk of developing metabolic syndrome
2. Study: Insomnia takes toll on tinnitus patients
3. Study: No link between depression, nasal obstruction
4. Study: More Pre-Teens Get Vaccines When Middle Schools Require Them
5. Study: Kids Who Sleep in Parents Bed Less Likely to Be Overweight
6. OHSU study: Misdiagnosis of MS is costing health system millions per year
7. UW study: Sleep apnea associated with higher mortality from cancer
8. Study: Heart damage after chemo linked to stress in cardiac cells
9. STeleR study: Telerehab improves functioning after stroke
10. Study: Willingness to be screened for dementia varies by age but not by sex, race or income
11. Study: 21 percent of newly admitted nursing home residents sustain a fall during their stay
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/19/2017)... ... February 19, 2017 , ... ... connected home healthcare, will join forces with Healthwise ® at HIMSS ... Healthwise, the industry leader in evidence-based health education, technology and services, will demonstrate ...
(Date:2/18/2017)... ... February 17, 2017 , ... Focused start-ups, not traditional health ... according to the recent NEJM Catalyst Insights Report on the New Marketplace. ... Insights Council, a qualified group of U.S. executives, clinical leaders, and clinicians at ...
(Date:2/18/2017)... ... February 17, 2017 , ... CONTACT:, Glenn ... Beverly Hills plastic surgeon Dr. Glenn Vallecillos experiments SculpSure, the hot, ... "Traditionally, plastic surgery has been centered around that idea that to achieve ones ...
(Date:2/18/2017)... ... February 18, 2017 , ... ProParagraph Fashion Volume 2 features ... ProParagraph Fashion Volume 2 for all multi-line FCPX project needs. Great for ... and choose from hand-crafted trend-setting designs with smooth animations that will add stylistic ...
(Date:2/17/2017)... ... February 17, 2017 , ... Smiles by Seese is a ... Davidson, NC. Dr. Brian Seese leads the practice as a skilled and highly credentialed ... roof. Smiles by Seese serves patients of all ages with excellence in general, restorative, ...
Breaking Medicine News(10 mins):
(Date:2/17/2017)... , Feb. 17, 2017  Perrigo Company plc (NYSE, TASE: ... U.S. Food and Drug Administration for hydrocodone bitartrate and homatropine ... Hydrocodone bitartrate and homatropine methylbromide oral solution ... the symptomatic relief of cough in adults and children 6 ... months ending January 2017 were approximately $16 million.   ...
(Date:2/17/2017)... Feb. 17, 2017   FormFast , the leader ... new partnership with Engage , one of the ... . FormFast will serve as the forms automation ... with MEDITECH .  FormFast is ... to complement and enhance the electronic health record. FormFast,s ...
(Date:2/16/2017)... Pa. , Feb. 16, 2017 Absorption ... biologics, and medical devices, is pleased to announce that ... has been selected as a winner of the 2017 ... SmartCEO Magazine and recognizes driven executives for their ... work ethic. The awards ceremony and celebration is on ...
Breaking Medicine Technology: