Researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute have designed an experimental drug that chokes off that sugar supply, causing the cells to self destruct.
The agent, called OSU-CG12, is an example of a new class of anticancer drugs called energy-restriction mimetic agents. It is described in a paper published recently in the Journal of Biological Chemistry.
“Energy restriction may offer a powerful new strategy for treating cancer because it targets a survival mechanism used by many types of cancer,” says principal investigator Ching-Shih Chen, professor of medicinal chemistry, of internal medicine and of urology.
“Our study proves that this new agent kills cancer cells through energy restriction. This is important because it shows that it is possible to design drugs that target energy restriction, and it is exciting because energy-restricting mimetic agents may also be useful for other diseases, including metabolic syndromes, diabetes, cardiovascular disease and obesity,” Chen adds.
Energy-restricting mimetic agents cause changes in cancer cells that are similar to those that occur in cancer cells deprived of their main energy source, the sugar glucose.
To design the new agent, Chen and his collaborators started with a drug called ciglitazone, which had been developed to treat type II diabetes but also showed anticancer activity in laboratory experiments.
That original drug produced its anti-diabetic effects by activating a protein called PPAR-gamma and a number of genes. The same mechanism was thought responsible for the drug’s anticancer effects. Chen and his colleagues showed, however, that the anticancer effects were due to a different mechanism, one involving energy restriction.
To enhance that activity, they altered the structure of the ciglitazone molecule, producing OSU-CG12. Using prostate cancer and breast cancer cell lines, they showed that the new Ohio State agent was 10 times better at killing cancer cells than ciglitazone and a second agent, the drug resveratrol, a natural product found in grapes and red wine that has weak anticancer activity and also works through energy restriction.
Furthermore, they showed that the new agent both stops glucose from entering cancer cells and suppresses the cells’ ability to metabolize the sugar.
Starved for fuel, the cancer cells begin consuming themselves, a process called autophagy – self eating – accompanied by other biochemical events that lead to the cells’ death by a natural process called apoptosis.
Chen and his colleagues continue modifying OSU-CG12 to enhance its efficacy. They also hope to test the agent in other conditions such as cardiovascular disease and Alzheimer’s disease.
Funding from the National Cancer Institute and the U.S. Department of Defense Prostate Cancer Research Program supported this research.
Chen is the Lucius A. Wing Chair of Cancer Research & Therapy, and a recipient of a 2010 Ohio State University Distinguished Scholar Award.
Other Ohio State researchers involved in this study were Shuo Wei and Samuel K. Kulp.
The Ohio State University Comprehensive Cancer Center- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (http://cancer.osu.edu) is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top 20 cancer hospitals in the nation, The James is the 180-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven funded programs in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.Darrell E. Ward
Darrell E. Ward | EurekAlert!
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences