Mayo researchers define celecoxib pathways and mechanisms for tumor reduction
The anti-inflammatory drug Celebrex, or celecoxib, reduces tumor mass by encouraging cell death and discouraging both cell proliferation and the sprouting of new blood vessels that feed growing tumors, according to a study reported in the November issue of Molecular Cancer Research.
The study, conducted by researchers at the Mayo Clinic College of Medicine in Scottsdale, Ariz., suggests this drug one day might be used to prevent and even treat breast tumors. Celebrex, marketed by Pfizer Inc., is a member of the general family of drugs that target the COX-2, an enzyme that plays a major role in arthritis pain and inflammation. "This COX-2 inhibitor represents a strong option for treatment of breast cancers, and a preventative agent for treatment of individuals with high risk of developing breast cancer or disease relapse," said Pinku Mukherjee, Ph.D., the senior author of the report.
The Mayo study showed that celecoxib caused reduction in mammary gland tumor mass that was associated with increased programmed cell death, or apoptosis, in the breast tissue of the mice. Celecoxib-induced cell death was associated with two molecular events involving pathways that lead to apoptosis. The COX-2 inhibitor increased expression of the Bax protein, which is known to function within the pro-apoptotic cell mechanism. Further, the introduction of celecoxib resulted in reduced activity of an anti-apoptotic protein, Akt, known to promote cell survival.
Generally, COX-2 works by regulating the production of prostaglandins in cells. In the Mayo study, celecoxib reduced levels of COX-2 protein in mammary tumor cells; the therapy was even more effective in minimizing the amounts of COX-2 dependent prostaglandin E metabolites in mammary tumor cells. "Celecoxib treatment appears to exert its antiproliferative, antiangiogenic, and pro-apoptotic effects by regulating the prostaglandin pathways," Mukherjee said. "This leads to the reduction in primary breast tumor mass." She noted that in an experiment with a limited number of mice, celecoxib appeared to completely inhibit metastasis of the breast tumor.
The study employed a mouse model system that closely resembles spontaneous breast cancer progression and metastasis in humans. "The MTag mouse model for human metastatic breast cancer is a helpful and important model in which to evaluate therapeutic strategies and to understand the mechanisms associated with therapy-induced growth inhibition," said Mukherjee. "This model allows us to proceed with preclinical studies that must precede clinical trials in order to enable us to develop efficient therapeutic strategies with targeted molecular therapies."
Contributing to this report along with Mukherjee were Mayo Clinic cancer researchers Gargi Basu, Ph.D., the lead author on the paper; as well as Sandra Gendler, Ph.D.; Latha Pathangey; M.S.,Teresa Tinder, B.S.; and Michelle LaGioia.
Russell Vanderboom, Ph.D. | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...