A powerful new strategy for treating cancer has been outlined by US scientists.
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.
Now, researchers 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.
"Energy restriction may offer a powerful new strategy for treating cancer because it targets a survival mechanism used by many types of cancer," said principal investigator Ching-Shih Chen.
"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 added.
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 colleagues 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.
The new study has been published in the Journal of Biological Chemistry.