Nav: Home

Estrogen-mimicking compounds in foods may reduce effectiveness of breast cancer treatment

January 11, 2018

LA JOLLA, CA - Jan. 11, 2018 - Scientists from The Scripps Research Institute (TSRI) have discovered that two estrogen-mimicking compounds found in many foods appear to potently reverse the effects of palbociclib/letrozole, a popular drug combination for treating breast cancer.

The study, published today in the journal Cell Chemical Biology, suggests that exposure to chemical compounds called xenoestrogens may significantly reduce the effectiveness of anti-estrogen treatments for cancer.

"Breast cancer patients taking palbociclib/letrozole should consider limiting their exposure to foods that contain xenoestrogens," says Gary Siuzdak, PhD, the study's senior author and senior director of TSRI's Scripps Center for Metabolomics.

The palbociclib/letrozole combination therapy was approved by the U.S. Food and Drug Administration in 2015 after a clinical trial showed it doubled the progression-free survival time in postmenopausal women with estrogen receptor (ER) positive, metastatic breast cancer. Letrozole blocks the production of estrogen, thus reducing the growth-promoting stimulation of ERs on breast cancer cells. Palbociclib blocks a different signaling pathway to impede cell division. The combination is now one of the standard therapies for ER-positive breast cancers.

Siuzdak and colleagues, including first and lead author Benedikt Warth, PhD, then a visiting Erwin-Schrödinger Fellow in the Siuzdak Lab, used advanced metabolomics technology to analyze the effects of palbociclib/letrozole on breast cancer cells. Metabolomics studies detail cells' metabolomes--populations of metabolites, the small-molecule end products of cellular processes.

"By profiling cell metabolomes with and without drug treatment we can get very useful information, for example about the biological pathways perturbed by the drug," says Siuzdak, a professor of chemistry, molecular and computational biology.

Their analysis revealed that neither palbociclib alone nor letrozole alone had a strong effect on metabolites in an ER-positive breast cancer cell line. However, the combination had a strikingly large impact. "The combination had a much more pronounced effect on cell-growth-related metabolites, which is consistent with the clinical trial results," Warth says.

Cancer researchers are increasingly concerned that xenoestrogens in food and water may enhance the growth of estrogen-fueled cancers, and may also hamper the effectiveness of anti-estrogen drugs such as letrozole. TSRI scientists therefore examined breast cancer cells treated with palbociclib/letrozole to see how their metabolite populations changed when they were also exposed to two common dietary xenoestrogens: zearalenone and genistein.

Zearalenone is produced by fungi that colonize maize, barley, wheat and other grains. It has been linked to birth defects and abnormal sexual development in pigs and other livestock, and is suspected of having caused an outbreak of early breast development among girls in Puerto Rico in the 1970s. Genistein is produced in certain plants including soybeans and is often highly concentrated in phytoestrogen-rich food supplements.

Even using very low doses, similar to typical dietary exposures, the researchers found that both model xenoestrogens largely reversed the metabolomic impact of the cancer drug combination. "This included many key metabolites," says Siuzdak.

Under the influence of either xenoestrogen, the breast cancer cells also resumed proliferating at a rate comparable to that seen in the absence of drug treatment.

"It's intriguing that even a low, background-level exposure to these xenoestrogens was enough to impact the effect of the therapy to this degree," says Warth, who is now an assistant professor at the University of Vienna's Department of Food Chemistry & Toxicology.

The results indicate that these dietary xenoestrogens do have the potential to affect cancer therapy outcomes--and genistein and zearalenone are just two of the many xenoestrogens commonly found in the human diet. "There's a high likelihood that other xenoestrogens would counteract the therapy in a similar way," Siuzdak says.

The impact of xenoestrogens on health and on hormonally-targeted therapies is nevertheless an understudied, underfunded area of research, the researchers emphasized.

"We generally know very little about the interactions of bioactive compounds we are exposed to through our food or the environment with drug treatments," Warth says. "So, in this field there are probably a lot of clinically relevant discoveries yet to be made."

"What I find intriguing is that metabolomics can be used to identify active metabolites that are therapeutically beneficial or, as in this case, exogenous fungal and plant metabolites that are detrimental," Siuzdak says. "Clearly, metabolites can have a significant impact in modulating therapeutics."
-end-
Other co-authors of the study, "Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy," were Philipp Raffeiner, Ana Granados, Tao Huan, Mingliang Fang, Erica M. Forsberg, and H. Paul Benton, all of The Scripps Research Institute at the time of the study; as well as Caroline H. Johnson at Yale University and Laura Goetz of the Scripps Clinic Medical Group.

Funding for the research came from the Austrian Science Fund (Erwin-Schrödinger fellowship awarded to Benedikt Warth), the George E. Hewitt Foundation for Medical Research and the National Institutes of Health (grants R01 GMH4368 and PO1 A1043376-02S1).

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists--including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine--work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www.scripps.edu.

Scripps Research Institute

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Jumpstarting Creativity
Our greatest breakthroughs and triumphs have one thing in common: creativity. But how do you ignite it? And how do you rekindle it? This hour, TED speakers explore ideas on jumpstarting creativity. Guests include economist Tim Harford, producer Helen Marriage, artificial intelligence researcher Steve Engels, and behavioral scientist Marily Oppezzo.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".