New research shows how antioxidants fuel the spread of lung cancer.
The researchers anticipate that these findings will lead to new treatments for lung cancer, which kills more people worldwide than any other cancer.
Cancer cells need lots of sugar, or glucose, to help them grow rapidly and metastasize, or spread. To meet this need, they use an energy-making process that is faster than the one that noncancerous cells use.
The downside of having this faster energy mechanism is that it produces lots of molecules called free oxygen radicals that place significant chemical stress on cells.
The new studies, which the researchers carried out using human tissue and mice, reveal how lung cancer cells use antioxidants to withstand oxidative stress and thrive.
The U.S. study shows how two genetic mutations help the lung cancer cells make their own antioxidants to overcome oxidative stress and metastasize.
The Swedish study shows how lung cancer cells use antioxidants from the diet to achieve the same outcome.
Antioxidants boost metastasis mechanisms
Both studies focus on the effect that reducing oxidative stress has on a protein called BTB domain and CNC homolog 1 (BACH1).
It appears that reducing oxidative stress through antioxidants can raise the stability of BACH1 and boost its accumulation in lung cancer cells.
BACH1 can trigger mechanisms that promote metastasis, one of which helps cancer cells acquire glucose from the blood and convert it into fuel.
"We hope these findings help to dispel the myth that antioxidants like vitamin E help to prevent every type of cancer," says Thales Papagiannakopoulos, Ph.D., an investigator on the U.S. study and an assistant professor in pathology at NYU School of Medicine in New York City.
Lung cancer is cancer that starts in the cells of the lungs. It is not the same as cancers that start elsewhere and then travel to the lungs to form secondary tumors or metastases.
Once cancer that starts in the lungs begins to metastasize, it spreads through the lymph nodes to the brain and other parts of the body.
Metastasis is the main reason why cancer is such a serious disease. Without metastasis, significantly fewer people would die of cancer.
Mutations help antioxidant production
There are two main types of lung cancer: small cell and the more common non-small cell.
Previous studies have shown that approximately 30% of non-small cell lung cancers flourish because their cells have acquired one of two types of mutation that promote antioxidant production. The new U.S. study investigated these mutations.
One of the two mutations that the U.S. team investigated raises levels of a protein called NRF2, which switches on genes that help lung cancer cells make antioxidants.
The other mutation that the U.S. team investigated switches off KEAP1, a protein that triggers the destruction of NRF2.
"We now have important new information on lung cancer metastasis," says Martin Bergo, senior author of the new Swedish study, "making it possible for us to develop new treatments, such as ones based on inhibiting BACH1."
Bergo is a professor in biosciences and nutrition at the Karolinska Institutet in Solna, Sweden. He headed the team behind the original 2014 studies that revealed that dietary antioxidant supplements, such as vitamin E, can hasten the growth of tumors.
He says that their new findings "show that the aggressive metastasizing induced by antioxidants can be blocked by stopping the production of BACH1 or by using drugs that suppress the breakdown of sugar."
"Our American colleagues," he adds, "show how inhibiting another enzyme, heme oxygenase, which is linked to BACH1, can also curb the metastasis process."
The researchers also believe that the findings reveal new insights into the faster mechanism that cancer cells use to make energy, which scientists call the Warburg Effect.
"For lung cancer patients, taking vitamin E may cause the same increases in cancer's ability to spread as the NRF2 and KEAP1 mutations that our team has linked to shorter survival."
Thales Papagiannakopoulos, Ph.D.