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Paper: Enzyme that digests vitamin A also may regulate testosterone levels

Editor’s note:  To contact Joshua W. Smith, email joshuasmith@jhu.edu

To contact John Erdman, email jwerdman@illinois.edu

The paper “Mice lacking B-carotene-15,15’-dioxygenase (BCO1) exhibit reduced serum testosterone, prostatic androgen receptor signaling, and prostatic cellular proliferation” is available online from the publisher or from the News Bureau.

Original story posted here: 
https://news.illinois.edu/blog/view/6367/437718 

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In new study, Illinois scientists trace activity of cancer-fighting tomato component

URBANA, Ill. – Years of research in University of Illinois scientist John Erdman’s laboratory have demonstrated that lycopene, the bioactive red pigment found in tomatoes, reduces growth of prostate tumors in a variety of animal models. Until now, though, he did not have a way to trace lycopene’s metabolism in the human body.

“Our team has learned to grow tomato plants in suspension culture that produce lycopene molecules with a heavier molecular weight. With this tool, we can trace lycopene’s absorption, biodistribution, and metabolism in the body of healthy adults. In the future, we will be able to conduct such studies in men who have prostate cancer and gain important information about this plant component’s anti-cancer activity,” said John W. Erdman Jr., a U of I emeritus professor of nutrition.

The U of I team began developing the tomato cultures that would yield heavier, traceable carbon molecules about 10 years ago. Erdman, doctoral student Nancy Engelmann, and “plant gurus” Randy Rogers and Mary Ann Lila first learned to optimize the production of lycopene in tomato cell cultures. They then grew the best lycopene producers with non-radioactive carbon-13 sugars, allowing carbon-13 to be incorporated into the lycopene molecules. Because most carbon in nature is carbon-12, the lycopene containing heavier carbon atoms is easy to follow in the body.

Soon after the carbon-13 technology was established, Engelmann, now Moran, took a postdoctoral research position at Ohio State University in the lab of medical oncologist Steven K. Clinton, and scientists at Illinois and Ohio State initiated human trials.

In this first study, the team followed lycopene activity in the blood of eight persons by feeding them lycopene labeled with the non-radioactive carbon-13. The researchers then drew blood hourly for 10 hours after dosing and followed with additional blood draws 1, 3, and 28 days later.

“The results provide novel information about absorption efficiency and how quickly lycopene is lost from the body. We determined its half-life in the body and now understand that the structural changes occur after the lycopene is absorbed,” Erdman explained.

“Most tomato lycopene that we eat exists as the all-trans isomer, a rigid and straight form, but in the bodies of regular tomato consumers, most lycopene exists as cis isomers, which tend to be bent and flexible. Because cis-lycopene is the form most often found in the body, some investigators think it may be the form responsible for disease risk reduction,” Moran explained.

“We wanted to understand why there is more cis-lycopene in the body, and by mathematically modeling our patients’ blood carbon-13 lycopene concentration data, we found that it is likely due to a conversion of all-trans to cis lycopene, which occurs soon after we absorb lycopene from our food,” she added.

The plant biofactories that produce the heavier, traceable lycopene are now being used to produce heavier versions of other bioactive food components. In another trial, phytoene, a second carbon-13–labeled tomato bioactive molecule, has been produced and tested in four human subjects.

“Our most recent project involves producing a heavy carbon version of lutein, found in green leafy vegetables and egg yolks. Lutein is known to be important for eye and brain health. In this case, we began with carrot suspension cultures and have already produced small quantities of ‘heavy-labeled’ lutein for animal trials,” Rogers said.

Right now, though, the Illinois–Ohio State team is excited about the new information the lycopene study has yielded. “In the future, these new techniques could help us to better understand how lycopene reduces prostate cancer risk and severity. We will be able to develop evidence-based dietary recommendations for prostate cancer prevention,” Erdman said.

This new journal article represents the most thorough study of lycopene metabolism that has been done to date, he added.

“Compartmental and non-compartmental modeling of ¹³C-lycopene absorption, isomerization, and distribution kinetics in healthy adults” appears pre-publication online in the American Journal of Clinical Nutrition. Authors are Nancy E. Moran, Morgan J. Cichon, Elizabeth M. Grainger, Steven J. Schwartz, Kenneth M. Riedl, and Steven K. Clinton of The Ohio State University; Janet A. Novotny of the USDA’s Human Nutrition Research Center; and John W. Erdman Jr. of the University of Illinois. The study was funded by the National Institutes of Health.

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Gene mapping reveals soy’s dynamic, differing roles in breast cancer

New research by doctoral candidate Yunxian (Fureya) Liu and nutrition professor William Helferich suggests that soy’s breast cancer preventive properties may stem from eating soy-based whole foods across the lifespan. Photo by L. Brian Stauffer. Click photo to enlarge.

4/28/2015 | Sharita Forrest, News Editor | 217-244-1072; slforres@illinois.edu

CHAMPAIGN, Ill. — Scientists have mapped the human genes triggered by the phytonutrients in soy, revealing the complex role the legume plays in both preventing and advancing breast cancer. 

Researchers at the University of Illinois found that the compounds in minimally processed soy flour stimulate genes that suppress cancer, while purified soy isoflavones stimulate oncogenes that promote tumor growth. The paper, available online, was accepted for publication in the journal Molecular Nutrition and Food Research.

Yunxian (Fureya) Liu, a graduate researcher in the laboratory of nutrition professor William G. Helferich, investigated more than 22,680 gene expressions in tumors collected from mice. The mice were injected with MCF-7 human breast-cancer cells and fed one of four diets – including one based on soy flour that contained mixed isoflavones, and another diet based on a purified isoflavone mixture. 

Each of these diets contained 750 parts per million of genistein equivalents, an amount comparable to that consumed by women eating a typical Asian diet. Genistein is the primary isoflavone in soy, and recent studies have raised concerns about its long-term effects and potential role in carcinogenesis.

Asian women’s risks for breast cancer tend to be three to five times lower than those of women in the U.S., which some researchers have attributed to Asian women’s consumption of soy-based whole foods, such as tofu and soy flour, across their lifespans. However, it’s unclear whether post-menopausal women in the West achieve similar protective benefits by consuming purified isoflavone supplements later in life.

In the current study, the mice’s ovaries had been removed to simulate post-menopausal women, and Liu found that the soy flour and purified isoflavone diets had differing effects on their cells’ expression of genes associated with breast cancer.

The mice that consumed soy flour exhibited higher expression of the tumor-suppressing genes ATP2A3 and BLNK, each of which is associated with suppressed tumor growth. These mice also expressed lower levels of oncogenes MYB and MYC, which researchers have found to be critical to tumor growth during early stage breast cancer, and associated with the uncontrolled proliferation of cancer cells, respectively.

“Most important, we found that the soy flour strengthened the whole immune function, which probably explains why it does not stimulate tumor growth,” said Liu, who is completing both a doctorate in human nutrition and a master’s degree in statistics.

Conversely, the purified isoflavones stimulated tumor growth by activating oncogenes MYB and MYC, while suppressing both immune function and antigen processing, the body’s natural process of seeking out and destroying cancer cells.

Liu correlated the gene expression of the tumor cells with that of women with breast cancer. She found that the purified isoflavones promoted the expression of two kinesin family genes, KIF14 and KIF23, each of which has been associated with shorter survival rates – i.e., less than five years. Accordingly, the isoflavone diet also decreased expression of zinc finger protein gene 423, also called ZNF423, which has been linked with survival rates of five years or greater among breast cancer patients.

Liu’s findings also support a hypothesis called the soy matrix effect, a theory that soy’s cancer preventive properties are derived from the interactions of complex bioactive compounds – other than isoflavones – within whole foods, such as soy flour.

“There was a difference in the biological responses of mice that consumed the soy flour and those that consumed isoflavone supplements, although both diets contained the same amount of the phytoestrogen genistein,” Liu said. “The findings suggest that it’s advisable for women with breast cancer to get isoflavones from soy whole foods, rather than isoflavone supplements.”

Helferich, a co-author on the paper, said purified isoflavones behave similarly to estrogens such as estradiol, which prior studies have linked with the growth and proliferation of breast cancer cells.

“The gene array data for the isoflavones look very similar to estradiol, which turns on many of the same genes, while the array data for the soy flour look somewhat like the negative control,” said Helferich, who has been studying the effects of soy for more than 20 years. “When the estradiol is removed, the tumors regress and almost become non-detectable. But with the soy flour, the tumors don’t grow or regress, so they’re not exactly like the negative control.” 

In another new study at Illinois, researchers found that soy isoflavones enhanced the growth of bone micro-tumors in mice with estrogen-responsive breast cancer, causing the tumors to metastasize more aggressively from bone to lung. Xujuan Yang, an associate researcher in Helferich’s laboratory, led that project. 

The mice that consumed an isoflavones diet had triple the number of tumors – and had larger tumors – on their lungs, compared with their counterparts in the control groups, Yang found. A paper on the study was published in the April issue of Clinical and Experimental Metastasis. 

“The main take-home message is, if you have breast cancer, isoflavone dietary supplements are not recommended,” Helferich said. “However, consuming soy from a whole food – along with other legumes – is likely safe.”

Editor’s note: To contact Yunxian Liu, call 217-265-50781 or e-mail yliu89@illinois.edu
To contact William Helferich, call 217-244-5414; e-mail helferic@illinois.edu


Original story by Sharita Forrest, University of Illinois News Bureau, found here:
http://news.illinois.edu/news/15/0428Soy_WilliamHelferich.html

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William G. Helferich

Dr. William G. Helferich

Food safety and toxicology; effect of natural chemicals present in foods on chronic diseases such as breast cancerDr. Helferich has research interests in the effect of phytochemicals on chronic diseases, and his focus is on the isoflavone genistein from soy, which acts as an estrogen. It is important for the general public to understand the importance of a healthy diet and not rely on chemicals to eliminate their bad eating habits.


Professor; helferic@illinois.edu; more detail here.


 

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Elvira de Mejia

Dr. Elvira de Mejia

Molecular mechanisms of chemoprevention of bioactive food components, mainly proteins and flavonoids, and their safety.We study food components with health benefits; analysis, characterization and mechanism of action of antimutagenic and anticarcinogenic compounds in foods (legumes, oilseeds and vegetables). We currently are working with bioactive proteins in different legumes. Our research group investigates the role of processing on the presence, concentration and physicochemical characteristics of proteins with biological potential against transformed human cells as well as their safety, such as allergenic potential. We also are studying the health benefits of tea, in particular the molecular mechanisms underlying the biological effects of ethnic teas used in folk medicine to combat several disorders, including cancer. This scientific study will introduce new materials to improve human health.


Professor; edemejia@illinois.edu; more detail here.


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Hong Chen

Dr. Hong Chen

Nutrient regulation of epigenetic modifications in cancer and other chronic diseases.The focus of my research is the role of epigenetic modifications on cancer and other chronic diseases. Epigenetic modifications of the genome, such as DNA methylation, histone methylation and acetylation, are powerful regulators of gene expression in mammalian cells. We are particularly interested in how epigenetic modifications are regulated by dietary components in colon tumor cells and how these modifications contribute to the tumorigenesis or cancer progression.  Currently the focus of my lab is on dietary folate and active components in soy foods and how they contribute to epigenetic regulations in colon cancer.


Associate Professor; hongchen@illinois.edu; more detail here.


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Elizabeth H. Jeffery

Dr. Elizabeth H. Jeffery

Biochemical and nutritional toxicology, with an emphasis on cancer prevention, is the focus of our laboratory. Epidemiological studies show that a diet rich in cruciferous vegetables, such as broccoli and Brussels sprouts, can lower the incidence of several cancers, including liver, prostate and colorectal. Our experiments identify how components in crucifers alter the synthesis of detoxification enzymes, resulting in more rapid clearance of deleterious compounds from the body before they can initiate a toxic or carcinogenic response. A major goal is to develop cruciferous vegetables with increased concentrations of chemopreventive agents and we work closely with an interdisciplinary group of 5 faculty to meet this goal. Experiments probing the mechanism of upregulation of detoxification enzymes apply molecular biology and biochemical enzyme assays to human and rodent liver cells in culture. Immunohistochemical and enzyme assay studies using purified chemicals or the whole vegetable fed to rodents confirm the findings from in vitro experiments. We have identified a synergism between two of the more abundant bioactive components in crucifers. The importance of this finding is two-fold: first that smaller doses of the vegetable should provide protection; and second that supplements containing the optimal mixture for protection could be formulated for individuals at high risk for cancer. These studies are being expanded to prostate, since prostate cancer is presently the most common cancer, with the second highest number of mortalities of any cancer, within the U.S. Functional foods; prevention of cancer through diet; role of detoxification enzymes in protection from cancer and toxicity.


Professor Emerita; ejeffery@illinois.edu; more detail here.


 

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John W. Erdman

Dr. John W. Erdman

Dietary factors that reduce the risk of prostate cancer, bioavailability of carotenoids, biological effects of carotenoid metabolites, influence of lutein and vitamin E on brain function, use of ultrasound techniques to detect prostate cancer progression and tissue alterations due to atherosclerosis or non-alcohol liver disease.


Professor Emeritus; jwerdman@illinois.edu; more detail here.


 

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Team to study health effects of botanical estrogens

Wild yam is among the many plants and plant extracts sold as “natural” treatments for the relief of menopausal symptoms. Creative commons photo by Marco Schmidt

Original story here.

9/7/2010 | Diana Yates, Life Sciences Editor | 217-333-5802; diya@illinois.edu

CHAMPAIGN, lll.— An ongoing research initiative into the health effects of botanical estrogens will get an $8 million boost from the National Institutes of Health.

“The types of botanical estrogens that are being marketed are getting more and more potent,” said William Helferich, a professor of food science and human nutrition at Illinois and director of the new center. “We want to see if they really are effective or detrimental.” U. of I. photo.

The Botanical Research Center, based at the University of Illinois, will draw on the expertise of a multidisciplinary team of researchers to address the many unknowns associated with use of botanical estrogens. These plants and plant-based compounds are often marketed as aids to prevent cancer, promote healthy aging or relieve menopausal symptoms. Researchers from Illinois, the University of Mississippi, Oregon State University and the FDA’s National Center for Toxicological Research will contribute to the five-year effort.

This is the second $8 million grant from the NIH to Illinois to conduct research into the health effects of botanical estrogens. The first five-year initiative focused on soy isoflavones, compounds found in soybean that previous studies indicated had potential as anti-cancer and cholesterol-lowering agents. That grant yielded studies that showed that the positive or negative health consequences of exposure to soy isoflavones depend on the timing of the exposure (whether it occurs in early, mid, or late life), tissue type (breast or brain, for example), and dose.

Many women take plant-based estrogens (also called phytoestrogens) that are advertised as natural – and, they presume, safer – alternatives to hormone-replacement therapy.

Foods, supplements and extracts made from soy, licorice root, wild yam and dong quai, for example, are believed to reduce the occurrence of hot flashes, improve sex drive, lower the incidence or prevent the recurrence of breast cancer, enhance mental function or treat other health problems.

Today, phytoestrogens are added to teas and energy drinks, used as food additives and marketed as nutritional supplements. The estrogenic components of the plants – such as the isoflavone genistein in soy – are often extracted and used in highly concentrated form.

Benita Katzenellenbogen, a professor of molecular and integrative physiology and of cell and developmental biology at Illinois, will lead a project to study the effects of botanical estrogens on gene activation and their interaction with estrogen receptors and regulatory proteins. U. of I. photo.

Research into their efficacy and safety has yielded mixed results. Consumption of some plants or extracts appears to reduce the risk of some cancers or minimize some of the unpleasant symptoms associated with menopause, while others have no effect. Still other studies, some of them conducted at Illinois, have found that certain phytoestrogens may actually induce cognitive problems, increase the recurrence of breast cancer and interfere with breast cancer treatment.

“The types of botanical estrogens that are being marketed are getting more and more potent,” said William Helferich, a professor of food science and human nutrition at Illinois and the director of the new center. “We want to see if they really are effective or detrimental.”

The new grant supports three projects led by Illinois faculty. The projects will explore whether and how phytoestrogens from soy, licorice root, dong quai and wild yam affect various tissues, influence gene expression or other cellular processes, increase or decrease the growth and metastasis of breast cancer tumors, influence bone loss or alter the rate of cognitive decline in aging. Two core areas will provide support to the three projects by authenticating and standardizing the botanical samples used in the studies and analyzing how the various compounds are utilized in the body.

Benita Katzenellenbogen, a professor of molecular and integrative physiology and of cell and developmental biology at Illinois, will lead a project to study the effects of botanical estrogens on gene activation and their interaction with estrogen receptors and regulatory proteins.

Helferich will lead a project to investigate the effects of botanical estrogens on bone, uterus and mammary glands, and their effects on the growth and progression of breast cancer and its metastasis to bone, lung or other tissues.

Illinois comparative biosciences professor Susan Schantz will serve as the associate director of the center and together with Illinois psychology professor Donna Korol and Oregon State University professors Russ Turner and Urszula T. Iwaniec will lead a project to study the effects of botanical estrogens on cognitive function and bone health.

Ikhlas Khan, of the University of Mississippi, will authenticate and standardize botanical samples used in the research.

Susan Schantz, professor of comparative biosciences, will serve as the associate director of the center. Photo by L. Brian Stauffer.

Daniel Doerge, of the FDA’s National Center for Toxicological Research, will identify and quantify the samples used in the study and determine appropriate dosing.

Editor’s note: To contact William Helferich, call: 217-244-5414; e-mail: helferic@illinois.edu.

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