Science Translational Medicine: Antioxidants Spur Tumor Growth in Mice

A new study using mouse tumors and human lung cancer cells helps explain why taking antioxidants could accelerate the growth of early tumors or precancerous lesions in high-risk populations.

A new study helps explain why taking antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations, like smokers. The findings published in the 29 January issue of Science Translational Medicine are mostly from experiments in mice, and further studies in humans will be needed to validate this effect.

Well-known antioxidants include vitamins A, C and E, as well as some medications. They are chemical compounds that delay some types of cell damage by preventing the buildup of molecules called reactive oxygen species, or ROS. For a long time scientists thought antioxidants could be useful for preventing cancer, but recent clinical trials in humans have hinted that antioxidants do not prevent lung cancer, and may actually increase cancer risk in certain high-risk groups.

The reason for this effect has been unclear, however. Studying two different antioxidants, vitamin E and a drug called acetylcysteine, Martin Bergö of the University of Gothenburg in Sweden and colleagues found that antioxidants sped up the progression of lung cancer in mice and in human cell lines.

 
Martin Bergö and Per Lindahl discuss the connection between antioxidants and tumor progression. | Elin Lindström Claessen

It's important to note that these findings do not point a finger at foods rich in antioxidants. The researchers specifically looked at doses found in potent multivitamins and dietary supplements.

"You would have to eat a lot of antioxidant-rich foods to get up to those levels," said Bergö during a 28 January press teleconference. And unlike supplements, foods contain other substances that may influence how antioxidants affect the body.

Mouse lung tumor tissue grows and becomes more invasive after exposure to antioxidants such as acetylcysteine (middle) and vitamin E (bottom. The top image is untreated tumor tissue. | AAAS/Science

The researchers used normal daily dietary doses of vitamin E and relatively low doses of acetylcysteine (humans typically receive acetylcysteine in an inhaled form, but the mice received it by mouth). When mice with early stages of lung cancer were given antioxidants, their tumors accelerated in growth, became more invasive, and killed the mice twice as fast compared to mice with early lung tumors that didn't receive antioxidants.

The antioxidants appear to boost cancer progression by decreasing the amount of a key tumor suppressor protein called p53. "When we knocked out p53 in the mice and in human lung cancer cell lines, the antioxidants had no effect," said Bergö.

The antioxidants may have achieved their deleterious effect by reducing ROS levels in tumors, which in turn would reduce levels of DNA damage. The reduced DNA damage might then lead to lower levels of p53.

The findings suggest that people carrying small undiagnosed tumors in the lungs (which may occur in anyone, but are more likely to be found in smokers) should avoid taking extra antioxidants because they may accelerate tumor progression. The researchers cautioned, however, that more studies are needed to confirm this.

Another implication concerns patients with a lung disease called chronic obstructive pulmonary disease (COPD). These patients take acetylcysteine to reduce mucus production in order to make it easier for them to breathe. The researchers believe the use of this antioxidant in COPD patients should be carefully evaluated.

Bergö and colleagues are looking into whether these findings apply to other types of cancer. Meanwhile, the jury is still out on the benefits of antioxidants in low-risk populations. "It is still not clear whether or not antioxidants in healthy people may reduce their future risk of lung cancer," Bergö said.