Compounds From Fruits, Vegetables And Grains Slow The Growth Of Human Tumor Cells

April 05, 1999

MADISON -- Researchers at the University of Wisconsin-Madison report in the current issue of the Journal of Nutrition that small concentrations of two compounds from plants we eat suppress the growth of three kinds of human cancer cells in the laboratory.

"Our studies showed that cancer cells were more sensitive to these compounds than normal cells and that the two compounds had a stronger effect when combined than we would have expected from the action of either alone," says Charles Elson, a nutritional scientist in the College of Agricultural and Life Sciences. "Our findings strengthen the idea that a diet rich in plants is beneficial because of the large array of plant compounds rather than the singular action of one kind of plant or one compound in plants."

Elson suggests that the anticarcinogenic activity of these and similar plant compounds differs from the mechanism of other agents that block or suppress cancer cell growth. Unless controlled, cancer cells typically live and divide indefinitely.

"The two compounds we studied suppress an enzyme," Elson says. "We think that this deprives tumor cells of chemical intermediates they need to multiply. The two compounds even work on human tumor cell lines that have mutations known to promote cancer."

Studies consistently have shown that people who eat a diet high in fruits, vegetables and grains have a reduced risk of many types of cancer, including lung, alimentary tract, liver, pancreas, bladder, kidney, breast, endometrium, cervix and prostate.

What is it about these foods that limits cancer? In a quest reminiscent of the search for vitamins begun in the last century, scientists are trying to identify the beneficial compounds in the fruits, vegetables and grains we eat that control tumor growth.

Plants contain many beneficial compounds including fiber and micronutrients such as vitamins and their precursors. According to Elson, research initially focused on compounds such as vitamin A, vitamin E and folic acid. But clinical trials with them have been inconclusive at best, he says.

Other scientists have been examining non-nutritive compounds in plants. Elson has been studying compounds he calls isoprenoids, a group that includes more than 22,000 compounds. All are derived from a parent compound called mevalonic acid. Limonene and lycopene are examples of isoprenoids that inhibit cancer.

Many isoprenoids contribute to plants' distinctive flavors and fragrances, Elson says. In plants, isoprenoids help regulate germination, growth, flowering, and dormancy while attracting pollinators and protecting plants from insects and fungi.

Elson began working with isoprenoids because some can reduce cholesterol levels in animals. Initially he hoped that depriving tumor cells of cholesterol would make them susceptible to cancer treatments. But Elson's early experiments showed he could not lower the cholesterol in tumor cells by feeding animals isoprenoids. However, he noticed that the isoprenoids slowed tumor growth.

To screen isoprenoids for those with anticarcinogenic activity, Elson tests them against a cell line developed from an extremely aggressive form of mouse melanoma. He has identified many isoprenoids that can slow the growth of this cell line. The tricky part has been finding isoprenoids that suppress cancer growth at the low concentrations that might occur in diets.

One such isoprenoid is gamma-tocotrienol, a compound found in cereal grains; it has a chemical structure related to vitamin E. In research published in 1997, Elson's group showed that substituting gamma-tocotrienol for vitamin E in a diet fed to mice slowed the growth of tumors transplanted to those mice. It was the first research demonstrating that an isoprenoid slowed cancer growth and prolonged the life of mice when fed at a level that an animal might consume.

In the current paper, Elson and his graduate student, Huanbiao Mo, found that gamma-tocotrienol slowed the growth of cell lines from human leukemia and breast cancer. They also tested beta-ionone -- an isoprenoid found widely in fruits and vegetables. Beta-ionone is related structurally to beta carotene, the precursor of vitamin A. Elson and Mo showed that beta-ionone also suppressed the growth of cell lines for human leukemia and breast cancer, as well as human colon cancer. The human cell lines were even more sensitive to the action of the isoprenoids than the mouse melanoma cells, according to Elson.

"We found that the human cancer cell lines were three times more sensitive to the isoprenoids than a non-cancerous cell line," Elson says. "This raises the issue of why cancer cells might be more sensitive to these plant compounds than non-cancerous cells."

Mo and Elson found that the isoprenoids interfered with the maturation of lamin B, a material cells need when they divide. Many of the tumor cells treated with the isoprenoids accumulated in a pre-division phase while many others entered apoptosis, or programmed cell death. The researchers showed that the isoprenoids suppressed the activity of 3 hydroxy-3-methyglutaryl coenzyme A (HMG CoA) reductase, an enzyme critical for the maturation of lamin B as well as the synthesis of cholesterol.

"We've known since the 1950s that tumor cells are more sensitive to reductions of HMG CoA reductase than healthy cells," Elson says. "When isoprenoids inhibit the activity of this enzyme they disrupt the processing of mevalonic acid via the mevalonate pathway. We think the tumor cells need chemical intermediates produced from the breakdown of mevalonic acid for lamin B maturation and that isoprenoids slow tumor growth by depriving tumor cells of those intermediates."

The nutritional scientist does not anticipate that his research will lead to a single critical isoprenoid or vegetable that people can eat to protect themselves from cancer. "These compounds act as a group to inhibit cancer growth," he says, "with some enhancing the effectiveness of others."

Nor does Elson believe in an exclusively vegetarian diet.

"I don't think that it's the presence of meat in diets that leads to health problems, but the lack of enough fruits, grains and vegetables. The people who eat a lot of animal products are often the same individuals that don't eat enough fruits and vegetables," he says. Writer: George Gallepp, 608-262-3636 ggallepp@facstaff.wisc.edu
-end-


University of Wisconsin-Madison

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.