Researchers found that the molecule – called resveratrol – is converted in the body to a known anti-cancer agent that can selectively target and destroy cancer cells.
Studies have suggested before that resveratrol might be cancer preventing, but this is the first time that scientists have gained an insight into the underlying mechanism of the chemical’s anti-cancer properties.
Prof Gerry Potter, the research group leader says: “Learning from nature in this way will help in our work to design drugs which are selectively activated in a tumour and can form the basis of anti cancer-treatments.
“Resveratrol is a defensive molecule against fungus in grapes and other crops, and is found at higher levels in those which have not been treated with man-made fungicides.
Researchers from the School of Pharmacy at Leicester’s De Montfort University found that resveratrol is processed by an enzyme (one of the cell’s factory workers) called CYP1B1, which is found on a variety of different types of tumours. This converts resveratol into a toxic product called piceatannol.
Previous research by the Leicester team has shown that this process is restricted to the tumour itself, limiting the toxicity to the cancer cells and serving to selectively destroy them.
Scientists previously believed that CYP1B1 was a cause of cancer, because it is only found in tumours and not in healthy tissue.
Far from causing cancer, they think the enzyme is there to fight it and the team is continuing research into ways to assist it in its work.
Prof. Potter says: “The belief that CYP1B1 is a cause of cancer is like blaming police for a crime just because they are on the scene. We suspected this natural product might be beneficial for health and have cancer preventative properties. This research shows just how it could prevent tumours developing by producing these anti-cancer molecules within the cancer cells themselves.”
Prof. Gordon McVie, Joint Director General for Cancer Research UK says: “Cancer Research UK has a long-standing interest in research into the use of natural products against cancer. The discovery that this molecule is converted into an anti-cancer agent within a tumour has important implications for research into prevention and treatment.”
Sir Paul Nurse, Joint Director General of Cancer Research UK says: “Specifically targeting cancer cells in order to destroy them is an important area of investigation which could ultimately lead to more effective drugs with fewer side effects.”
- British Journal of Cancer86 (5)
Resveratrol is classified as a polyphenol or as a phyto-oestrogen because of its structural similarity to the oestrogen estradiol.
Piceatannol is a closely related phyto-estrogen with known anti-cancer activity and is a tyrosine kinase inhibitor.
The enzyme CYP1B1 belongs to the cytochrome P450 enzyme family and is highly represented in human tumours. It has been found in a wide range of tumours including brain, breast, colon, lung and ovary, but was not detected in the corresponding normal tissues (Murray et al 1997). CYP1B1 is known to catalyse estradiol to 4-hydroxyestradiol.
The group hypothesised that resveratrol might be converted by the enzyme CYP1B1 because of its similarity in structure to estradiol.
The team are also looking into the beneficial effects of brassica family vegetables (e.g. broccoli, cabbage etc.) which contain a molecule that activates the CYP1B1 enzyme.