New study results from researchers at the Swiss Federal Institute of Technology Lausanne (Switzerland) suggest that copper is essential for energy production in malignant cells and that reducing levels of bioavailable copper can slow tumor growth in mice.

The trace element copper is key to cell growth because of its role in energy production through respiration. Cell growth requires energy, which is stored molecularly as adenosine triphosphate (ATP) after being produced by either respiration or glycolysis. Respiration is the more efficient of the two processes but involves several enzymes, one of the most important of which requires copper for its activity. Its role in cellular energy production may help to explain why copper is important in cancer. As cancer cells typically undergo rapid proliferation, their energy requirements are greater than those of normal cells. Indeed, copper imbalances have previously been associated with cancer as well as other diseases.

Seiko Ishida, who led the new study along with Douglas Hanahan, explained in a press release, “This study was motivated by our previous puzzling observation...that cancers, unlike healthy tissues, are especially sensitive to changes in systemic copper levels.”

To investigate the association between copper and cancer, the researchers used genetically engineered mice that develop pancreatic neuroendocrine tumors. They exposed some of the mice to copper by spiking their drinking water with copper at the maximum levels permitted in public water supplies by the US Environmental Protection Agency (20 μM). In a second group of mice, they reduced systemic copper levels using the copper-chelating drug tetrathiomolybdate. Copper exposure accelerated tumor growth in mice, whereas copper insufficiency reduced tumor growth (Proc. Natl. Acad. Sci. USA published online 11 November 2013; doi:10.1073/pnas.1318431110). Copper-deficient tumors seemed to be compensating for a lack of copper by using glycolysis rather than respiration to produce energy but were unable to produce sufficient ATP and did not grow.

The results provide evidence that copper can enhance the proliferation of cancer cells, “indicating that copper is an essential nutrient for them,” according to Ishida.

If the same holds true for tumors in humans, then controlling copper levels in cancer patients could be clinically beneficial. Ishida and Hanahan's team proposes that minimizing systemic copper levels, combined with blocking glycolysis, could offer a two-step strategy to 'starve' cancer cells by limiting the two major pathways for ATP production. Animal studies should be developed to evaluate the therapeutic potential for such a strategy.