Navigation Links
Inhibiting key enzymes kills difficult tumor cells in mice
Date:8/15/2011

Tumors that do not respond to chemotherapy are the target of a cancer therapy that prevents the function of two enzymes in mouse tumor cells, according to Pennsylvania medical researchers.

"We've known for well over a decade that when tumors become hypoxic they become resistant to chemotherapy and radiotherapy," said Wafik S. El-Deiry, M.D. Ph.D., American Cancer Society Research Professor, Rose Dunlap Professor and chief of hematology/oncology, Penn State College of Medicine. "This is a huge problem in the treatment of patients with cancer. As tumors progress, they have regions that are not well perfused with blood vessels and tumors become hypoxic."

A hypoxic tumor lacks oxygen because there are not enough blood vessels within the tumor to allow red blood cells to transport oxygen throughout the tumor.

El-Deiry and his team report in a recent issue of Cancer Research that the drug sangivamycin-like molecule 3 (SLM3) helps keep tumor cells from multiplying in lab mice.

Treating a tumor with SLM3 inhibits two kinase, or enzymes: GSK-3, which regulates cell growth and cell death, and CDK1, which regulates cell division and blood vessel growth. Tumor cells treated with SLM3 become more sensitive to chemotherapy and die, according to El-Deiry and his colleagues.

"If you just inhibit GSK-3, that may not be enough and not necessarily desirable," said El-Deiry, who is also the associate director for translational research, Cancer Institute. "But there's something fortuitous about the dual targeting of these two kinases, (GSK-3 and CDK-1), with respect to cancer therapy. If you inhibit these two kinases, the dual inhibition works together to kill hypoxic tumor cells.

"While pure inhibition of GSK-3 can promote cell proliferation, the combination of GSK-3 and CDK-1 inhibition not only inhibits cell proliferation but also promotes cell death," El-Deiry added.

To find SLM3, the researchers screened a chemical library looking for molecules that induce apoptosis -- cell death -- in hypoxic tumor cells. SLM3 does that, and the researchers found eight molecules whose structures were similar.

SLM3 was the version that induced the most cell death in concert with TRAIL, a naturally occurring molecule in the body that tells a cell it is time to die. TRAIL sets a process in motion that targets and shuts down tumor cells and keeps them from spreading.

SLM3, a nucleoside analog, helps keep tumor cells from multiplying by stopping cells before they duplicate their DNA. Nucleosides are the building blocks of nucleic acids and molecules like ATP -- the energy source for the body. A nucleoside analog competes with ATP and inhibits kinases, like GSK-3 and CDK1.

GSK-3 helps regulate cell growth and cell death. CDK1 decreases the tumor's ability to divide and generate more blood vessels. SLM3 inhibits both these kinases.

"The bottom line is the molecules actually work to shrink tumors when these molecules are combined with chemo or TRAIL therapy," El-Deiry said. "We think that these are important observations that need to be tested further in the clinic."


'/>"/>

Contact: Victoria M. Indivero
vmi1@psu.edu
814-865-9481
Penn State
Source:Eurekalert

Related medicine news :

1. Inhibiting fatty acids in immune cells decreases atherosclerosis risk
2. Inhibiting prostate cancer without disturbing regular body processes
3. Researchers find that inhibiting microRNAs may help prevent degenerative eye disorders
4. New evidence that smokeless tobacco damages DNA and key enzymes
5. Heart Enzymes May Predict Outcome After Bypass Surgery
6. New York Truck Driver Watching Porn Kills Mother, Appalls Personal Injury Lawyers Such As David Perecman
7. Cognitive Skills May Shrink With Tamoxifen
8. Stethoscope App gives iPhone New Clinical Skills
9. Paper Kills 2.0 Book by Center for Health Transformation Features Chapter by StatCom
10. PeopleStreme Collaborates with SkillSoft for Learning Management Content
11. New agent chokes off energy supply, kills cancer cells
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... Beach, CA (PRWEB) , ... June 25, 2016 , ... ... UCLA with Magna Cum Laude and his M.D from the David Geffen School of ... Diego and returned to Los Angeles to complete his fellowship in hematology/oncology at the ...
(Date:6/25/2016)... ... June 25, 2016 , ... Conventional wisdom preaches the benefits ... terms of the latter, setting the bar too high can result in disappointment, perhaps ... slow progress toward their goal. , Research from PsychTests.com reveals that ...
(Date:6/24/2016)... ... 2016 , ... June 19, 2016 is World Sickle Cell Observance Day. In ... benefits of holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued ... Sickle Cell Disease (SCD) is a disorder of the red blood cells, which can ...
(Date:6/24/2016)... ... , ... Global law firm Greenberg Traurig, P.A. announced that 20 Florida attorneys ... peers for this recognition are considered among the top 2 percent of lawyers practicing ... members of this year’s Legal Elite Hall of Fame: Miami Shareholders Mark D. ...
(Date:6/24/2016)... ... 2016 , ... Topical BioMedics, Inc, makers of Topricin and MyPainAway Pain Relief Products, join The ... raise to $12 an hour by 2020 and then adjusting it yearly to increase at ... the minimum wage, assure the wage floor does not erode again, and make future increases ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... ITASCA, Ill. , June 23, 2016  In a startling ... states are failing their residents by lacking a comprehensive, proven plan ... , a definitive ranking of how states are tackling the ... rating to only four states – Kentucky , ... and Vermont . Of the 28 failing states, ...
(Date:6/23/2016)... , June 23, 2016 Research and ... News Issue 52" report to their offering. ... influenza treatment creates a favourable commercial environment for MedImmune to ... patient base that will serve to drive considerable growth for ... would serve to cap sales considerably, but development is still ...
(Date:6/23/2016)... , June 23, 2016  Astellas today announced the establishment of Astellas Farma Colombia (AFC), a new affiliate ... in Latin America . ... ... ... ...
Breaking Medicine Technology: