Several clinical studies have shown that taking the anti-inflammatory drug celecoxib can reduce the risk of developing polyps that lead to colon cancers, at the cost of increasing the risk of heart disease. But what if this tradeoff was not necessary?
Researchers at Winship Cancer Institute of Emory University have identified a way that celecoxib (Celebrex) pushes cancer cells into suicide, separately from its known effects. The Winship team’s results outline a route to alternatives to celecoxib that keep its cancer-preventive properties while avoiding its risks.
Celecoxib’s risk profile has confined its use to people who have inherited cancer risk or those who have had cancer already. Its effectiveness at stopping tumor progression and recurrence is being tested in several clinical trials for people who have had lung, head and neck and other types of cancer.
Shi-Yong Sun, PhD, and colleagues report in an upcoming issue of the journal Cancer Research that celecoxib inhibits an enzyme called GSK3 (glycogen synthase kinase 3) in lung cancer cells. This causes the disappearance of a protein called c-FLIP, which usually staves off apoptosis, a form of cellular suicide.
“We have been focusing on how celecoxib induces c-FLIP degradation and apoptosis in cancer cells, independent of COX-2 inhibition,” Sun says.
Scientists think that celecoxib’s ability to inhibit COX-2 enzymes is the basis for its anti-inflammatory properties as well as its influence on heart disease. In cell culture, some chemical relatives of celecoxib have been shown to have anticancer effects without inhibiting COX-2.
Sun is professor of hematology and medical oncology at Emory University School of Medicine and a Georgia Cancer Coalition Distinguished Cancer Scholar. The first author of the paper, postdoc Shuzhen Chen, is now at the Chinese Academy of Medical Sciences’ Institute of Medicinal Biotechnology in Beijing. Fadlo Khuri, MD, deputy director of Winship Cancer Institute, is a co-author on the paper.
The result was surprising partly because until a few years ago, scientists thought that inhibiting GSK3, while possibly helpful in diseases such as diabetes, could promote cancer. However, recent results suggest that blocking GSK3 may stop cell growth in prostate, pancreatic and colon cancers and some types of leukemia.Sun cautions: “We do not know whether GSK3 inhibition by celecoxib has anything to do with celecoxib’s cardiovascular risk.”
The research was supported by the Georgia Cancer Coalition, the Department of Defense and the National Institutes of Health.
S. Chen, W. Cao, P. Yue, C. Hao, F.R. Khuri and S.Y Sun. Celecoxib promotes c-FLIP degradation through Akt-independent inhibition of GSK3. Cancer Res. Online ahead of print. (2011).
The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service.Learn more about Emory’s health sciences:
Holly Korschun | EurekAlert!
Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications
Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine