Scientists Say Apigenin Compound Found in Foods Takes
Away Power of Cancer Cells to Survive
Abundant in Mediterranean diet that makes cancer
May 21, 2013 - New research suggests that a
compound called apigenin, abundant in the Mediterranean diet, takes away
the "superpower" of cancer cells to escape death. 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 programming. This study in cells, led by Ohio State University
researchers, found that this compound in certain plant-based foods –
apigenin - could stop breast cancer cells from inhibiting their own
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,
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.
Parsley, celery and chamomile tea are the most
common sources of apigenin, but it is found in many fruits and
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 Andrea Doseff, associate professor of 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."
Doseff oversaw this work with co-lead author Erich
Grotewold, professor of molecular genetics and director of Ohio State's
Center for Applied Plant Sciences (CAPS). 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 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
"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 other."
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
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. The nature
of the splice ultimately influences which protein instructions the mRNA
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,"
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 first author Daniel
Arango, a Ph.D. student in the Molecular, Cellular and Developmental
Biology graduate program; and Kengo Morohashi, Alper Yilmaz, Arti
Parihar and undergraduate Bledi Brahimaj of the Department of Molecular
Genetics, all at Ohio State; and Kouji Kuramochi of Kyoto Prefectural
University in Japan. Doseff, Arango and Parihar are affiliated with Ohio
State's Division of Pulmonary, Allergy, Critical Care and Sleep