Antioxidants and cancer – the plot thickens

What role do antioxidants play in cancer?

Are antioxidants good for you? Many people believe that the answer to this question is yes, and some think that antioxidants might even help prevent cancer. We’ve posted about this before, and as yet the evidence is far from conclusive – at least as far as cancer’s concerned.

Now new research is set to make matters more complicated. A paper published last month in the journal Nature suggests antioxidants may actually help keep cancer cells alive. This doesn’t mean that supplementing your diet with antioxidants or eating foods that contain them will cause cancer, but it certainly shows that there isn’t yet a clear idea of how antioxidants are involved in the disease.

Could antioxidants fuel the growth of cancer?

The researchers were looking at what happens to normal breast cells when they move away from their usual surroundings. Normally, when cells in the body drift away from their usual environment, they receive signals forcing them to commit ‘cell suicide’. This prevents them from growing in the wrong place.

But some cancer cells don’t obey this rule. They’re often able to move around the body and cause new tumours far from where the original cancer began. Because cancer spread, or metastasis, causes most deaths from the disease, it’s a crucial process for cancer researchers to understand.

To find out more, the scientists at Harvard Medical School, Massachusetts, grew breast cells in a 3D structure similar to that of a human breast.

Normal breasts are made up of many tiny sacs, each with an outer layer of cells encased by a membrane, surrounding a hollow centre. Cells that detach from the membrane and move into the centre usually self-destruct.  But in breast cancer, the hollow centre slowly fills with cancer cells that are somehow able to survive.

Cell starvation

The researchers showed that normal breast cells that have detached from the membrane have changes in their metabolism (the way they use energy). These detached cells make cutbacks in the amount of glucose they’re taking up, leading to reduced levels of the cell’s ‘fuel’, ATP. This is a sign of cellular ‘starvation’, which eventually goes on to kill these errant wanderers.

So how do cancer cells escape starvation and cheat death? The changes that turn a normal cell into a cancer cell involve certain genes called ‘oncogenes’. The researchers wanted to find out how one particular oncogene – HER2, which is overactive in many breast cancers – affected breast cells that have moved away from their usual place.

The scientists compared the behaviour of normal breast cells with those expressing too much HER2. They discovered that overactive HER2 allowed the detached cells to maintain their glucose uptake, saving them from starvation.

So what about the antioxidants?

In an unexpected twist, the researchers also showed that ‘cell starvation’ in wandering cells leads to a situation called oxidative stress. Ultimately this means the cells fill with free radicals – molecules that can cause damage to DNA and other parts of the cell. And this is where things get really interesting – the researchers found that if the starving cells were treated with the antioxidants N-acetyl cysteine or Trolox, it reversed the damage, allowing the cells to survive.

Although this work was done in a highly artificial system, it’s certainly intriguing, and suggests that antioxidants, in some circumstances, could actually fuel the growth of cancer cells that have moved away from their normal surroundings. These results raise questions about how cancer spreads and how antioxidants might be involved in this process. Obviously the conclusion that antioxidants might promote cancer is highly speculative – but then so is much of the work by which antioxidants’ supposed benefits are claimed.

So are antioxidants good or bad?

These new results paint a confusing picture, suggesting that antioxidants may have two conflicting roles when it comes to cancer:

1. They may, in theory, help to decrease the risk of cancer by mopping up free radicals (although concrete evidence for this remains elusive, as we mentioned before).
2. They might also assist in the survival of cancer cells that have moved away from their normal environment.

As the authors say, their results could help us to understand why some trials of antioxidants have suggested that they can sometimes increase the risk of cancer. They might also shed light on the recent paper that showed antioxidant supplements can interfere with cancer treatment. But the full story isn’t clear yet.

As so often happens in science, these new results have shown us just how much we don’t know. More research will be needed before we understand the complex relationship between cancer and antioxidants.

Lisa Faulkner

References:

Schafer, Z. et al (2009). Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment Nature, 461 (7260), 109-113 DOI: 10.1038/nature08268

Gottlieb, E. (2009). Cancer: The fat and the furious Nature, 461 (7260), 44-45 DOI: 10.1038/461044a

Omenn, G. et al (1996). Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease New England Journal of Medicine, 334 (18), 1150-1155 DOI: 10.1056/NEJM199605023341802

Labriola D, & Livingston R (1999). Possible interactions between dietary antioxidants and chemotherapy. Oncology (Williston Park, N.Y.), 13 (7) PMID: 10442346