How antioxidants could fight prostate cancer - genes reveal clues

By Dominique Patton

- Last updated on GMT

Related tags: Prostate cancer, Cancer, Antioxidant

US scientists have discovered a molecular pathway in mice that
makes prostate cells vulnerable to the free radicals that lead to

The pathway, which is also involved in human prostate cancer, may help researchers find out whether antioxidants can prevent prostate cancer.

The team from Johns Hopkins Kimmel Cancer Center and The Cancer Institute of New Jersey found that a defect in the tumour suppressor gene Nkx3.1 causes prostate cells to lose the ability to protect themselves from oxygen damage.

"Normally, cells with functioning Nkx3.1 seem to process oxidative free radicals appropriately,"​ said Theodore L. DeWeese, a co-author of the study published in the August issue of Cancer Research​.

"But cells with faulty Nkx3.1 genes cannot manage oxidative injury. Then, their DNA gets damaged, and that leads to other mutations that in turn can bring about cancer."

The researchers specifically found that a key role of Nkx3.1 is to prevent oxidative damage by regulating the expression of other genes.

Prostate cancer is the most commonly diagnosed cancer in men in the EU and America and is second to lung cancer as the leading cause of cancer death. It accounted for 15 per cent of male cancers in the EU during 2004 and 238,000 new cases, according to the International Agency for Research on Cancer (IARC).

Significant funding has been invested in studies investigating ways of preventing such high incidence, including some research into antioxidant vitamins and plant-derived chemicals that are thought to protect against free radicals.

These are highly reactive atoms with an unpaired electron that are produced as a result of normal body metabolism, and are widely believed to be closely involved in ageing, as well as cancer development.

Several studies suggest that vitamin E, lycopene and green tea may offer some protection against cancer. The new research on mice could allow researchers to clarify these initial findings.

"Our findings provide new insights regarding the relationship between loss of protection against oxidative stress and the initiation of prostate cancer,"​ added Cory Abate-Shen, senior study author.

"One key finding is that defects in the oxidative response pathway occur early in prostate cancer development."

For the study, the researchers used gene expression profiling to compare the genetic makeup of mice whose Nkx3.1 gene was disrupted with that of normal mice.

Mice with malfunctioning Nkx3.1 incorrectly expressed 638 genes, including those that created a significant reduction in some antioxidant enzymes vital to oxidative damage prevention. These alterations occurred in mice as early as four months of age - well before cellular changes are visible in the mouse prostate.

The mutant mice also displayed a fivefold increase in the amount of cancer-related DNA damage, called 8-hydroxy-2'-deoxyguanosine.

Further investigation showed that the progression to prostate cancer as it occurs in mice lacking Nkx3.1 and another tumour suppressor, Pten, correlated with additional deregulation of antioxidants and more profound accumulations of oxidative damage to DNA and protein.

"Mice with defective Nkx3.1 provide a valuable tool for preclinical studies to test whether antioxidants might be useful for prostate cancer prevention,"​ Abate-Shen said.

Continuing studies will test antioxidants or other agents on the altered mice.

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