Flavonoids Kill Human Pancreatic Cancer Cells

Two researchers at the University of Illinois (UIC; Chicago, IL, USA) examined the inhibitory effects of flavonoids, limonoids, phenolic acids, and ascorbic acid citrus fruit bioactive compounds on BxPC-3 and PANC-1 human pancreatic cancer cells in vitro, focusing on the antiproliferative mechanism of action of the flavonoid apigenin as related to the glycogen synthase kinase-3β (GSK-3β) nuclear factor kappa B signaling pathway.

The researchers found that apigenin inhibited the GSK-3β enzymatic pathway, leading to a decrease in the production of antiapoptotic genes in the pancreatic cancer cells, thus encouraging the cancer cells to self-destruct via apoptosis. In one of the cancer cell lines, the percentage of cells undergoing apoptosis went from 8.4% in cells that had not been treated with the flavonoid to 43.8% in cells that had been treated with a 50-micromolar dose. Treatment with the flavonoid also modified gene expression, causing upregulation of certain genes associated with pro-inflammatory cytokines such interleukin 17. The study was published on August 13, 2013, in Molecular Nutrition and Food Research.

“Apigenin alone induced cell death in two aggressive human pancreatic cancer cell lines. But we received the best results when we pretreated cancer cells with apigenin for 24 hours, then applied the chemotherapeutic drug gemcitabine for 36 hours,” said study coauthor professor Elvira de Mejia, PhD. “Pancreatic cancer patients would probably not be able to eat enough flavonoid-rich foods to raise blood plasma levels of the flavonoid to an effective level. But scientists could design drugs that would achieve those concentrations.”

“The trick seemed to be using the flavonoids as a pretreatment instead of applying them and the chemotherapeutic drug simultaneously. 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,” added coauthor Jodee Johnson, PhD. “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.”

Flavonoids are a class of plant secondary metabolites that may modify allergens, viruses, and carcinogens, and demonstrate significant antioxidant activity in vitro that may be stronger than those of vitamin C and E. However, inside the human body, they have little or no direct antioxidant value, since flavonoids are poorly absorbed (less than 5%), with most of what is absorbed being quickly metabolized and excreted.

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