Compound derived from fruit and vegetables could be used to improve the effects of an established cancer drug

Oct 5 2004

A food extract could be used to improve the effects of an established cancer drug, scientists report in the British Journal of Cancer.

The drug, mitomycin C (MMC), is a well-known anticancer treatment used mainly against solid tumours in the bladder and lower bowel. It is activated by enzymes naturally found in the human body, but its use is limited by severe side effects at higher doses.

Canadian scientists have now used a natural compound, derived from fruit and vegetables, to stimulate tumour cells so that they produce more of one enzyme that activates MMC. Their research raises the prospect of a pill that could be taken alongside MMC to reduce patients' side effects.

MMC damages the DNA in tumour cells, stopping them from dividing and growing. The drug, like most chemotherapy drugs, is associated with a number of side effects, the most serious of which relate to the production of blood cells in the bone marrow.

One relatively common side effect is anaemia, which is a drop in the number of red blood cells that sometimes requires a blood transfusion. White blood cell counts can also fall, increasing the patient's risk of serious infections.

MMC is activated by enzymes occurring naturally throughout the body, the most important of which is called NQO1. This enzyme is usually produced at higher levels in tumours compared to normal tissues, giving researchers a potential new way to target MMC treatment to cancer cells and reduce impact to healthy organs.

Dr Asher Begleiter and colleagues at the Manitoba Institute of Cell Biology, a joint institute of CancerCare Manitoba and the University of Manitoba, wanted to see if they could further increase the amount of NQO1 in tumour cells, thereby improving the anticancer activity of MMC specifically where it is needed.

Mice with tumours were fed either normally or on a diet containing dimethyl fumarate (DMF), a metabolite of fumaric acid, which is found in fruit and vegetables. The researchers then looked to see whether the DMF diet increased NQO1 activity and, as a result, enhanced the anticancer effect of MMC.

Dr Begleiter says, "Our results show that DMF given with MMC significantly reduced the size of tumours compared to MMC alone or no treatment at all. It gives us a bigger bang for our buck when using mitomycin C, which should allow us to treat patients with lower doses.

"The activating enzyme NQO1 is induced by several compounds. We chose DMF because of its natural origin and the fact that we could easily administer it in the diet, but there might be even better candidates for future clinical use."

Other possible inducing agents include extracts from vegetables such as broccoli and cauliflower. Similarly, there are other drugs in development that, like MMC, are activated by NQO1. If a dietary supplement is developed that successfully induces NQO1 in tumours, it is probable that it will enhance the activity of these new drugs as well.

Dr Begleiter adds, "We're hoping to start clinical trials in the near future to test the potential of this therapeutic strategy. Given the range of potential inducers of NQO1, and the increasing number of drugs that are activated by it, there's every hope we will find a successful combination."

Dr Lesley Walker, Director of Cancer Information at Cancer Research UK, says, "Mitomycin C has been used for many years to treat certain forms of cancer. This study shows that it may be possible to achieve the same anticancer effect with lower doses, which means fewer and less severe side effects for patients."