Two laboratory studies found that the flavonoids apigenin and luteolin, found in celery, artichokes and herbs like Mexican oregano, kills human pancreatic cancer cells in vitro by inhibiting an important enzyme.
Pancreatic cancer is a very aggressive cancer, and there are few early symptoms, meaning that the disease is often not found before it has spread. It is the fourth leading cause of cancer-related deaths, with a five-year survival rate of only 6 percent. Ultimately the goal is to develop a cure, but prolonging the lives of patients would be a significant development. The scientists say their study is the first to show that apigenin treatment can lead to an increase in interleukin 17s in pancreatic cells, showing its potential relevance in anti-pancreatic cancer activity.
Pancreatic cancer patients couldn't eat enough flavonoid-rich foods to raise blood plasma levels of the flavonoid to an effective level but it might be possible to design drugs that would achieve those concentrations.
The researchers used the flavonoids as a pre-treatment instead of applying them and the chemotherapeutic drug simultaneously, said co-author Jodee Johnson, PhD from the University of Illinois.
"Apigenin alone induced cell death in two aggressive human pancreatic cancer cell lines. But we received the best results when we pre-treated cancer cells with apigenin for 24 hours, then applied the chemotherapeutic drug gemcitabine for 36 hours," said Elvira de Mejia, a University of Illinois professor of food chemistry and food toxicology.
"Even though the topic is still controversial, our study indicated that taking antioxidant supplements on the same day as chemotherapeutic drugs may negate the effect of those drugs," Johnson said. "That happens because flavonoids can act as antioxidants. One of the ways that chemotherapeutic drugs kill cells is based on their pro-oxidant activity, meaning that flavonoids and chemotherapeutic drugs may compete with each other when they're introduced at the same time."
The scientists found that apigenin inhibited an enzyme called glycogen synthase kinase-3β (GSK-3β), which led to a decrease in the production of anti-apoptotic genes in the pancreatic cancer cells. Apoptosis means that the cancer cell self-destructs because its DNA has been damaged.
In one of the cancer cell lines, the percentage of cells undergoing apoptosis went from 8.4 percent in cells that had not been treated with the flavonoid to 43.8 percent in cells that had been treated with a 50-micromolar dose. In this case, no chemotherapy drug had been added.
Treatment with the flavonoid also modified gene expression. "Certain genes associated with pro-inflammatory cytokines were highly upregulated," de Mejia said.
Citation: Jodee L. Johnson and Elvira Gonzalez de Mejia, 'Flavonoid apigenin modified gene expression associated with inflammation and cancer and induced apoptosis in human pancreatic cancer cells through inhibition of GSK-3β/NF-κB signaling cascade', Molecular Nutrition&Food Research 14 AUG 2013, DOI: 10.1002/mnfr.201300307