Chemists at the Welsh School of Pharmacy in Cardiff said that prostate cancer is usually treated with hormonal therapy, but at some point the cancer generally becomes resistant to this treatment.
It has been recognized for some time that vitamins A and D might have a therapeutic effect in hormone-refractory prostate cancer by suppressing the growth of cancer cells and restoring the control of cell growth that is lost in cancer. However, the researchers noted that the vitamins are metabolised quickly in the body and so do not stay around long enough to exert any anticancer effect.
"The vitamins A and D are metabolised by two cytochrome enzymes - CYP24 (for vitamin D) and CYP26 (for vitamin A)," said the research team. "Prostate cancer cells also contain these enzymes and are able to avoid the vitamins' differentiating effects."
The study therefore is looking at a series of compounds called tetralones that the scientists have synthesised and then tested in rat cell systems, where they found that two of the compounds, the CYP24 and 26 enzymes, were inhibited.
Although, their investigations into ways to prevent the fast metabolism of these vitamins are still at an early stage, the Cardiff team is upbeat about initial results.
"An enzyme inhibitor could act indirectly as an anticancer agent by preventing the breakdown of the differentiating agents vitamins A and D," said reasercher Sook-Wah Yee. "In theory, such a compound might be able to be used as combination treatment with the vitamins."
One drug known to block CYP24 and 26 is ketoconazole. The researchers reported that the tetralones displayed greater or similar inhibitory activity than ketoconazole for both CYP24 and CYP26.
They will now investigate the activity of the new compounds in prostate cancer cell lines and if positive results are achieved, further tests will be carried out to assess whether the new drugs have greater enzyme selectivity than ketoconazole.
Prostate cancer is one of the biggest cancer killers in industrial countries and affects more than 500,000 men worldwide every year. This number is expected to increase with the ageing population.