Could genistein, a soy component, be a key element in the development of better breast cancer treatments?
In the past, some components of soy have been linked to various health benefits, including relief of acute menopausal symptoms such as hot flashes.
At the core of some of these benefits stand isoflavones, which are plant-derived, estrogen-like compounds that can influence estrogen receptors once ingested.
Now, new research from the University of Arizona Cancer Center in Tucson looks at the potential of genistein — a soy isoflavone — in halting the development of breast cancer tumors.
The researchers' findings were recently published in the journal Current Developments in Nutrition.
BRCA1 'silencing' promotes cancer
Tamoxifen, an estrogren agonist — meaning that it acts by binding to estrogen receptors — is a drug often used to treat and prevent cancer. However, many breast cancer tumors are estrogen-receptor-negative, which renders hormonal therapy ineffective since these tutors lack the expression of the estrogen receptor.
"In triple-negative breast cancers," says Dr. Romagnolo, "no targeted chemotherapy is available."
Triple-negative breast cancer has a very poor outcome, as it is particularly aggressive and resistant to most available therapies. Thus, finding a way of addressing the lack of an estrogen receptor might provide new avenues for tackling this disease.
The BRCA1 gene plays a central role in the development of breast cancer. In a healthy system, it has a suppressive role, protecting against the development of cancerous tumors. When BRCA1 "malfunctions," the first line of defense against cancer is weakened.
In yet other cases, gene methylation — a process in which methyl groups are added to the genetic code — affects BRCA1 activity, rendering it "silent." Thus, the BRCA1 gene becomes unable to act as a tumor suppressor.
Can BRCA1 be 'unsilenced?'
For the purpose of this study, the researchers focused on the relationship between the aromatic hydrocarbon receptor (AhR) — which is a protein activated by environmental carcinogenic factors such as tobacco smoke — and BRCA1.
They note that activated AhR "silences" BRCA1, rendering it harmless to cancer cells, which, in turn, leaves tumors free to develop and spread.
Dr. Romagnolo notes that normally, BRCA1 interacts with estrogen receptor-alpha (ER-alpha). When BRCA1 is "silenced," however, the connection with ER-alpha is also compromised. So, drugs that would normally act on the BRCA1-ER-alpha interaction — of which tamoxifen is one — become ineffective.
Thus, Dr. Romagnolo and team were interested in seeing whether or not they could disable the effect of activated AhR, to allow BRCA1 to regain normal function.
'Lifetime soy intake tied to lower cancer risk'
This is where soy-derived genistein comes into play. Dr. Romagnolo remarks that the consistent consumption of soy foods has been linked to lower breast cancer risk, and this was the element that provided the main clue.
"Lifetime intake of soy in Asian women has been linked to reduced risk of breast cancer. Genistein is the predominant isoflavone found in soy and it may actually block DNA methylation."
Dr. Donato F. Romagnolo
The team conducted in vitro experiments using cancer cells taken from human breast tumors, which led them to believe that genistein might, as expected, be effective in "unsilencing" the BRCA1 gene.
These initial efforts confirmed genistein's potential in breast cancer treatment, allowing BRCA1 to continue acting as a tumor suppressor and renewing the interaction between it and ER-alpha. This context would also allow tamoxifen to act effectively upon cancer tumors.
Dr. Romagnolo and team's next step will be to see if they can replicate these results in experiments in vivo, using mice, in the hope that — should the further studies be successful — they will be able to move on to clinical trials in humans.
The researchers are also interested in gaining a better understanding of the potential of soy foods in preventing breast cancer. It is important to find out which soy-based foods, in what quantities, and consumed at what point in life would boost protection against cancer.
Another unknown, they add, is whether or not gestational exposure of the fetus to genistein could offer lifelong benefits to the baby.