Compounds found in food products such as soy can reverse the effects of a widely used breast cancer treatment, researchers have discovered.
In a paper in the journal Cell Chemical Biology, scientists from the Scripps Institute in California, US, warn that plant-derived oestrogen-mimicking compounds, found in several types of food and collectively called phyto-oestrogens, halt the effects of a combination therapy that involves two drugs, palbociclib and letrozole. They extended their warning to cover similar compounds found in some types of fungi (and called therefore myco-oestrogens), which sometimes enter the food chain via infected cereal crops.
Collectively, oestrogen mimickers from all sources are called xeno-oestrogens.
The combination of palbociclib (PAL) and letrozole (LET) is used to treat postmenopausal women with oestrogen receptor positive, metastatic breast cancer.
While neither drug used on its own produces strong results, the combination treatment (approved by the US Food and Drug Administration in 2015) has been shown to significantly reduce cancer cell growth and increase survival periods for many patients.
In their research, however, the Scripps team, headed by Benedikt Warth, used laboratory populations of ER-positive breast cancer cell lines and exposed them to each of the target drugs, individually and in combination, and then to two oestrogen-mimics – zearalenone, derived from fungus, and genistein, found in soy.
The team used a metabolomics approach, using mass spectrometry to assess and measure small molecules known as metabolites. These are the end products of cellular activity. Metabolomics regards them as a reliable measure of the response of biological systems to genetic or environmental change.
The first part of the research reconfirmed that the two drugs worked much better in combination. Letrozole blocks the production of oestrogen, thus reducing the stimulation of oestrogen-receptors on cancer cells. Palbociclib works by disrupting a signalling pathway that left unchecked promotes cell division.
Adding zearalenone or genistein to cells lines treated with the two drugs produced remarkable and concerning results.
“Proliferation of both cell lines was markedly reduced after exposure to PAL+LET, when compared to untreated cells,” the researchers write. “Strikingly, co-administration of PAL+LET with either of the two xeno-oestrogens GEN or ZEN restored cell proliferation to levels that were comparable to non-treated cells.”
In other words, the fungus and soy derivatives stopped the drugs in their tracks. Warth and his colleagues, however, caution that much more research is needed to fully understand the results. There are epidemiological studies, they report, that find a correlation between high soy diets and reduced incidence of breast cancer.
The role of diet in relation to cancer risk and treatment is complex, they say, and clear causation difficult to establish. Asian women, they point out, generally consume much higher amounts of soy products than their Western counterparts, raising the possibility that age of first exposure to phyto-oestrogens might be significant.
Nevertheless, says co-author Gary Siuzdak, a risk-averse approach to foods containing oestrogen mimics might be wise.
“”Breast cancer patients taking palbociclib/letrozole should consider limiting their exposure to foods that contain xeno-oestrogens,” he says.
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