Compound in Veggies May Increase Effectiveness of Cancer Treatment

By John Gever
RIVERSIDE, Calif., 02 nov 2008A flavonoid compound found in many fruits and vegetables may make cancers more sensitive to standard DNA-damaging treatments, researchers here said.
Cultured neuroblastoma cells were more likely to die after dosing with etoposide if they were pretreated with the flavonoid, called apigenin, reported Xuan Liu, Ph.D., and Xin Cai, Ph.D., of the University of California Riverside, online in the Proceedings of the National Academy of Sciences.
The researchers said apigenin appears to work by restoring the p53 tumor-suppressor protein's normal function in cancer cells where the protein has been rendered inactive.
When fully functioning, p53 forces cells with DNA damage that cannot be repaired to undergo apoptosis. Its deactivation allows cancer cells to survive DNA-damaging treatments such as certain chemotherapies and radiation.
Dr. Liu said the study supported inclusion of more vegetables and fruits in the diet to prevent cancer, although it did not address whether the apigenin in foods exerts the same effect in vivo.
The researchers also suggested that other compounds using the same p53-targeted mechanism could be developed that have stronger treatment-sensitizing effects.
The specific action of apigenin is that it inhibits phosphorylation of p53 by another protein called Thr-55, the researchers said.
When this phosphorylation takes place, p53 is ejected from the cell nucleus and destroyed.
Treatment with apigenin, Drs. Liu and Cai found, restores p53's nuclear localization and allows it to trigger apoptosis in response to DNA damage.
But apigenin was not wholly effective in the etoposide-treated neuroblastoma cells.
Pretreatment with apigenin raised the rate of apoptosis to 53%, compared with 20% in cells dosed only with etoposide.
Previous research had found that apigenin inhibits growth of tumor cell lines in vitro, but its mechanism was unknown, Drs. Liu and Cai said.
Earlier studies had also indicated apigenin does not affect normal human cells, "suggesting that perhaps this dietary flavonoid is not toxic to non-transformed cells and thus could be used to specifically sensitize cancers caused by abnormal cytoplasm localization of wild-type p53," they added.
The study was funded by the National Cancer Institute.
No potential conflicts of interest were reported.
Primary source: Proceedings of the National Academy of SciencesSource reference:Cai X, et al "Inhibition of Thr55 phosphorylation restores p53 nuclear localization and sensitizes cancer cells to DNA damage" PNAS 2008; DOI: 10.1073/pnas.0804608105.