by Emily Caldwell
May 20, 2013
New research suggests that
a compound abundant in
the Mediterranean diet
takes away cancer cells' "superpower" to
Scientists Design ‘Fishing’ Technique
to Show How Foods Improve Health.
(Credit: © M.studio /
By altering a very specific step in gene
regulation, this compound essentially re-educates cancer cells into
normal cells that die as scheduled.
One way that cancer cells thrive is by inhibiting a process that
would cause them to die on a regular cycle that is subject to strict
This study in cells, led by Ohio State University
researchers, found that a compound in certain plant-based foods,
called apigenin, could stop
breast cancer cells from inhibiting their own death.
Much of what is known about the health benefits of nutrients is
based on epidemiological studies that show strong positive
relationships between eating specific foods and better health
outcomes, especially reduced heart disease.
But how the actual molecules within
these healthful foods work in the body is still a mystery in many
cases, and particularly with foods linked to lower risk for cancer.
...are the most common sources of
apigenin, but it is found in many fruits and vegetables.
The researchers also showed in this work that apigenin binds with an
estimated 160 proteins in the human body, suggesting that other
nutrients linked to health benefits - called "nutraceuticals"
- might have similar far-reaching effects.
In contrast, most pharmaceutical drugs
target a single molecule.
"We know we need to eat
healthfully, but in most cases we don't know the actual
mechanistic reasons for why we need to do that," said said
Andrea Doseff, associate
internal medicine and
molecular genetics at Ohio
State and a co-lead author of the study.
"We see here that the beneficial
effect on health is attributed to this dietary nutrient
affecting many proteins. In its relationship with a set of
specific proteins, apigenin re-establishes the normal profile in
cancer cells. We think this can have great value clinically as a
potential cancer-prevention strategy."
Andrea Doseff oversaw this work
with co-lead author
professor of molecular genetics and director of Ohio State’s
Center for Applied Plant Sciences
The two collaborate on studying the
genomics of apigenin and other flavonoids, a family of plant
compounds that are believed to prevent disease.
The research (Molecular
Basis for the Action of a Dietary Flavonoid Revealed by the
Comprehensive Identification of Apigenin Human Targets)
appears this week in the online early edition of the journal
Proceedings of the National Academy of Sciences.
Though finding that apigenin can influence cancer cell behavior was
an important outcome of the work, Grotewold and Doseff point to
their new biomedical research technique as a transformative
contribution to nutraceutical research.
They likened the technique to "fishing" for the human proteins in
cells that interact with small molecules available in the diet.
"You can imagine all the potentially
affected proteins as tiny fishes in a big bowl. We introduce
this molecule to the bowl and effectively lure only the truly
affected proteins based on structural characteristics that form
an attraction," Doseff said.
"We know this is a real partnership
because we can see that the proteins and apigenin bind to each
Through additional experimentation, the
team established that apigenin had relationships with proteins that
have three specific functions. Among the most important was a
protein called hnRNPA2.
This protein influences the activity of messenger RNA, or mRNA,
which contains the instructions needed to produce a specific
protein. The production of mRNA results from the splicing, or
modification, of RNA that occurs as part of gene activation.
nature of the splice ultimately influences which protein
instructions the mRNA contains.
Doseff noted that abnormal splicing is the culprit in an
estimated 80 percent of all cancers. In cancer cells, two types of
splicing occur when only one would take place in a normal cell - a
trick on the cancer cells' part to keep them alive and reproducing.
In this study, the researchers observed that apigenin's connection
to the hnRNPA2 protein restored this single-splice characteristic to
breast cancer cells, suggesting that when splicing is normal, cells
die in a programmed way, or become more sensitive to
"So by applying this nutrient, we
can activate that killing machinery. The nutrient eliminated the
splicing form that inhibited cell death," said Doseff, also an
investigator in Ohio State's
Davis Heart and Lung Research Institute.
"Thus, this suggests that when we
eat healthfully, we are actually promoting more normal
splice forms inside the cells in our bodies."
The beneficial effects of nutraceuticals
are not limited to cancer, as the investigators previously showed
that apigenin has anti-inflammatory activities.
The scientists noted that with its multiple cellular targets,
apigenin potentially offers a variety of additional benefits that
may even occur over time.
"The nutrient is targeting many
players, and by doing that, you get an overall synergy of the
effect," Grotewold explained.
Doseff is leading a study in mice,
testing whether food modified to contain proper doses of this
nutrient can change splicing forms in the animals' cells and produce
an anti-cancer effect.
Additional co-authors are,
Doseff, Arango and Parihar are
affiliated with Ohio State’s
Division of Pulmonary, Allergy, Critical Care
and Sleep Medicine.