Antioxidants such as vitamin C found to spur cancer growth & metastasis

A new study has found that antioxidants like vitamins C and E activate a mechanism that stimulates the growth of new blood vessels in cancer tumors, helping them to grow and spread. The researchers say their findings highlight the potential risk of taking antioxidant supplements when they’re not needed.

To grow and metastasize, cancer tumors need a constant supply of oxygen- and nutrient-rich blood. And that requires the formation of new blood vessels from existing ones, a process called angiogenesis. When tissues are starved of oxygen (hypoxia), cancer cells in the affected area send chemical signals to get the endothelial cells that line the blood vessels to form new vessels.

A new study by researchers at Sweden’s Karolinska Institutet has examined mechanisms of angiogenesis and found that antioxidants play an unexpected role in the growth and spread of tumors.

“We’ve found that antioxidants activate a mechanism that causes cancer tumors to form new blood vessels, which is surprising since it was previously thought that antioxidants have a protective effect,” said Martin Bergö, the study’s corresponding author. “The new blood vessels nourish the tumors and can help them grow and spread.”

Normally, antioxidants scavenge free oxygen radicals from the body’s cells and prevent or reduce the damage caused by oxidative stress. Oxidative stress is known to damage DNA and regulate the progression of various cancers, including those of the breast, lung, liver, colon, prostate, ovary and brain.

“There’s no need to fear antioxidants in normal food, but most people don’t need additional amounts of them,” said Bergö. “In fact, it can be harmful for cancer patients and people with an elevated cancer risk.”

The researchers had shown previously that antioxidants like vitamins C and E accelerated the growth and spread of lung cancer by stabilizing a protein called BACH1. The protein is activated when the levels of free oxygen radicals in the body drop, which can happen when extra antioxidants are introduced into the diet, or when spontaneous mutations occur in tumors, activating the production of antioxidants.

In the current study, the researchers conducted most of their work on lung cancer using organoids with lung cancers cultivated from patients, but also did studies on mice and samples of human breast and kidney tumors. They found that tumors in which BACH1 was activated, either by the ingestion of antioxidants or by overexpression of the BACH1 gene, produced more new blood vessels and were highly sensitive to angiogenesis inhibitors.

Angiogenesis inhibitor drugs are used to treat cancer, but the effects are varied, and they can produce nasty side effects.

“Many clinical trials have evaluated the efficacy of angiogenesis inhibitors, but the results have not been as successful as anticipated,” said Ting Wang, the study’s lead author.

The researchers found that BACH1 can also induce angiogenesis by a mechanism that doesn’t require hypoxia; that is, tumors can form new blood vessels in the presence of normal oxygen levels. They also found that BACH1 is regulated similarly to the protein hypoxia-inducible factor 1-alpha (HIF-1-alpha), whose expression has been implicated in angiogenesis-driven tumor growth and metastasis, suggesting that the two proteins work together.

“Our study opens the door to more effective ways of preventing angiogenesis in tumors,” Wang said. “For example, patients whose tumors exhibit high levels of BACH1 might benefit more from anti-angiogenesis therapy than patients with low BACH1 levels.”

The researchers are already looking ahead to future studies.

“The next step is to examine in detail how levels of oxygen and free radicals can regulate the BACH1 protein, and we will continue to determine the clinical relevance of our results,” said Wang. “We’ll also be doing similar studies in other cancer forms such as breast, kidney and skin cancer.”

The study was published in The Journal of Clinical Investigation.

Source: Karolinska Institutet