Diabetes drug combined with glycolysis inhibitor effective in
killing cancer cells
13 September 2011
Blocking a key controller of
energy production in cancer cells and treating them with the diabetes
drug metformin effectively starves cancer cells, according to research
published in Nature Cell Biology .
One of the key characteristics of cancer cells is their ability
to divide and grow quickly. To do this they need to switch to a
method of producing energy rapidly, which breaks down glucose in a
process called glycolysis. By doing this they generate the energy
and raw materials needed to create new cells.
The researchers found that this switching is controlled by a
protein complex called NF-kB, which controls the balance between
different types of energy generation. When glucose supplies run
short, NF-kB moves energy generation to an alternative process that
doesn’t rely on glucose. But blocking NF-kB in cancer cells leaves
them unable to make this switch and so they ultimately die.
By targeting this protein complex, the researchers showed they
could kill bowel cancer cells in the lab. To mimic the effect of
glucose starvation, the researchers first treated the cancer cells
with a molecule that blocks NF-kB, though by itself it has no effect
on survival. But when combined with the diabetes drug metformin,
which blocks alternative methods of energy production, they
effectively besiege the cancer cells so that they starve and die.
Professor Guido Franzoso, lead researcher based at Imperial
College London, said: “This is the first time that NF-kB has been
shown to control how cells generate energy. We already knew that
NF-kB plays a role in cancer. It is part of a family of regulators
that control the immune and inflammation responses and have been
shown to promote the disease.
“Inhibitors of NF-kB are currently used in the clinic to treat
cancer patients but have had limited success, due to their side
effects. We hope that we can now start exploring the possibility of
combining them with metformin as a double hit to increase their
effectiveness against cancer.”
Dr Julie Sharp, senior science information manager at Cancer
Research UK, said: “Cancer cells need a rapid supply of energy to
grow and divide and understanding how they generate energy is an
exciting area of research. By blocking energy production,
effectively starving the cells, researchers have revealed a new way
to selectively attack cancer cells leaving normal cells unharmed.”
1. Mauro, C et al. NF-kB controls energy homeostasis and
metabolic adaptation by upregulating mitochondrial respiration.
Nature Cell Biology, 2011. Published online 28 August 2011.