Fight cancer with cold

Fighting cancer with cold

MISE À DAY

Study finds that cold temperatures activate heat-producing brown fat, which hogs the sugar needed for the development of several types of cancer.

Cancer cells often reprogram their metabolism to promote growth and survival. One of these adaptations, used by several types of cancers, is to metabolize large amounts of glucose by fermentation to generate energy in the form of ATP, a phenomenon known as the Warburg effect. 

This production of ATP is however 18 times less efficient than that using the complete oxidation of glucose at the level of the mitochondria (energy-producing cellular units) and therefore requires a constant supply of glucose from the environment surrounding the tumors to support the tumor growth. Harnessing this dependence on glucose to block cancer progression therefore represents an attractive cancer-fighting strategy.

Heat-producing adipocytes

A roundabout way of starving cancer cells of sugar is to activate other glucose-consuming cells. Brown adipose tissue cells are good candidates in this sense: these adipocytes possess the property of burning energy from sugar and fatty acids in the bloodstream thanks to their very high content of mitochondria (this is incidentally this high amount of mitochondria which gives the cells their brown appearance). Brown adipose tissue mitochondria specifically contain a protein called thermogenin which prevents metabolism from generating chemical energy (ATP) from sugar and fats and instead causes heat to be produced.

Cancer doesn't like the cold

Since brown adipose tissue is activated by cold, a team of researchers1 first compared the growth of different types of cancers (colorectal, breast and pancreatic) in mice exposed to hot or cold temperatures. They observed that mice acclimatized to temperatures of 4°C had significantly slower tumor growth and lived almost twice as long as mice that lived in rooms at 30°C.

Using imaging tests to examine glucose metabolism, the researchers found that cold temperatures triggered significant glucose uptake in brown adipose tissue, while glucose signals were barely detectable in tumor cells. It therefore appears that cold-activated brown adipose tissue competes with tumors for glucose and may help inhibit tumor growth.

Subsequent experiments go in this direction: for example, when the researchers eliminated brown fat or even thermogenin from the animals, the beneficial effect of exposure to cold was abolished and the tumors grew at a comparable rate. those exposed to higher temperatures. They also observed that a diet high in sugar canceled the effect of cold temperatures and allowed cancers to progress normally.

Cold treatment

To determine if exposure to cold caused similar effects in humans, researchers recruited six healthy volunteers and one cancer patient being treated with chemotherapy.

Using positron emission tomography (PET), researchers first found that regular exposure (six hours a day for two weeks) to slightly cold room temperature (16°C) led to a significant amount of activated brown fat in the neck, spine and chest.

The cancer patient was exposed to temperatures of 22 oC for a week, then 28  ;oC for four days. Imaging scans detected an increase in brown fat and a decrease in glucose uptake by the tumor during the lower temperature compared to the higher temperature.

Collapse room temperature could therefore prove to be an extremely simple means of improving the effectiveness of cancer treatments. To paraphrase an old saying, beat cancer while it's cold!

1. Seki T et al. Brown-fat-mediated tumor suppression by cold-altered global metabolism. Nature, published on August 3, 2022.