Compound in Mediterranean diet aids cancer cell death

A compound abundant in the Mediterranean diet re-educates cancer cells into becoming normal cells that die as scheduled, a new study has found.
Ohio State University researchers found that the compound in certain plant-based foods, called apigenin, could stop breast cancer cells from inhibiting their own death.
Parsley, celery and chamomile tea are the most common sources of apigenin, but it is also found in many fruits and vegetables.
The researchers found 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.
"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," said Andrea Doseff, associate professor of internal medicine and molecular genetics at Ohio State and a co-lead author of the study.

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. The nature of the splice ultimately influences which protein instructions the mRNA contains.
Doseff noted that abnormal splicing is the culprit in an estimated 80 per cent 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 chemotherapeutic drugs.

"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," Doseff said.
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.
The research was published in the journal Proceedings of the National Academy of Sciences.