Indole-3-carbinol (I3C), a phytochemical found naturally in cruciferous vegetables like broccoli and cauliflower, and genistein, a soy isoflavone, were shown to have potential prevention activity against hormone-responsive tumours, such as breast, ovarian and prostate cancer.
Epidemiological and animal studies have shown that diets high in such vegetables resulted in less instances of certain cancers, while a trial supplementing the diet with I3C reported the prevention of oestrogen-dependent tumours. This led researchers to test the effect of I3C, and genistein, on human breast and prostate cancer cell cultures.
The targets of the studies were the so-called breast cancer susceptibility genes, BRCA1 and BRCA2. Both of these genes produce proteins, also called BRCA1 and BRCA2, which are responsible for repairing damaged DNA in cells. Cells with defective copies of the disease are unable to repair the gene, risking mutation and tumour formation.
"BRCA1 and BRCA2 have been identified as tumour suppressors for several different hormone-responsive cancer types," explained lead researcher Eliot Rosen in the British Journal of Cancer (vol. 94, pp.407-426).
The study, performed by researchers at Georgetown University, Washington DC, added specific doses of I3C, or genistein, or both, to human breast and prostate cancer cells and measured the levels of BRCA1 and BRCA2 proteins.
"These studies show reproducible induction of BRCA1 and BRCA2 by I3C, with increases in BRCA1 and BRCA2 protein levels at an I3C dose of 60 micromoles at 24 hours of five to ten fold for the breast cancer cell lines and eight to sixteen fold for the prostate cancer cell lines," wrote lead author S. Fan.
When genistein was studied independently, a five-micromole dose increased BRCA levels four to twelve fold for breast cancer cells, and five to seventeen fold for the prostate cancer cells.
When the researchers introduced a combination of I3C (25 micromoles) and genistein (one micromole) they observed a "greater effect on BRCA induction than either agent alone."
The mechanism by which I3C and genistein can protect against cancer is proposed to be via an endoplasmic reticulum (ER) stress-like pathway. The ER is an organelle found in eukaryotic cells that is responsible for, amongst other things, protein modification. By stressing the ER, BRCA is induced and thereby protects against DNA damage.
"It is now clear that the function of crucial cancer genes can be influenced by compounds in the things we eat. Our findings suggest a clear molecular process that would explain the connection between diet and cancer prevention," said Prof Rosen.
Further study is needed to investigate toxicity levels that may be associated with higher doses, and then to take the intervention out of cell cultures and into human clinical trials.
Professor John Toy, medical director of Cancer Research UK, said: "We still don't know if this is exactly how these chemicals might act in every day life.
"Diet's role in cancer prevention is complex. This research explores an interesting hypothesis as to how certain components of diet can affect cancer risk. The evidence is building that these chemical compounds act on some of the genes inside cells that help prevent cancer developing.