Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Agent Chokes Off Energy Supply, Kills Cancer Cells

08.04.2010
Cancer cells grow so fast that they can outstrip their blood supply, leaving them short of oxygen. The cells then produce energy in a way that needs less oxygen but more sugar.

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
Medical Center Communications
614-293-3737
Darrell.Ward@osumc.edu

Darrell E. Ward | EurekAlert!
Further information:
http://www.osumc.edu

More articles from Life Sciences:

nachricht Nerves control the body’s bacterial community
26.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Ageless ears? Elderly barn owls do not become hard of hearing
26.09.2017 | Carl von Ossietzky-Universität Oldenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The fastest light-driven current source

Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.

Graphene is up to the job

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Nerves control the body’s bacterial community

26.09.2017 | Life Sciences

Four elements make 2-D optical platform

26.09.2017 | Physics and Astronomy

Goodbye, login. Hello, heart scan

26.09.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>