The Plant Flavonoid Luteolin Blocks Insulin-Like Growth Factor Signaling in Colon Cancer Cells

Luteolin, a flavonoid commonly found in fruit and vegetables, has been shown in a recent study to decrease IGF-II (insulin-like growth factor) production and down regulate insulin-like growth factor-I receptor (IGF-IR) signaling in HT-29 human colon cancer cells.

The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system consists of two cell-surface receptors (IGF-IR and IGF-IIR), two ligands (IGF-I and IGF-II), a family of six high-affinity IGF-binding proteins (IGFBP 1-6), as well as associated IGFBP degrading enzymes,

Dietary sources of luteolin include celery, green pepper, thyme, perilla, chamomile tea, carrots, olive oil, peppermint, rosemary, navel oranges, and oregano. Preclinical studies have shown that luteolin may possess pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. From preliminary research, the ability of luteolin to inhibit angiogenesis, to induce apoptosis, to affect carcinogenesis in animal models, to possibly reduce tumor growth in vivo, and to sensitize tumor cells to the cytotoxic effects of some anticancer drugs suggests that this flavonoid may have cancer chemopreventive and chemotherapeutic potential.

Investigators at Hallym University (Chuncheon, Korea) had previously shown that luteolin reduced HT-29 cell growth by inducing apoptosis and cell cycle arrest. The objective of their new study was to examine whether luteolin down regulated the insulin-like growth factor-I receptor (IGF-IR) signaling pathway in HT-29 cells.

In order to assess the effects of luteolin and/or IGF-I on the IGF-IR signaling pathway, cells were cultured with or without luteolin and/or IGF-I. Cell proliferation, DNA synthesis, and IGF-IR mRNA levels were evaluated by a cell viability assay, radioactive thymidine incorporation assays, and real-time polymerase chain reaction, respectively. Western blot analyses, immunoprecipitation, and in vitro kinase assays were conducted to evaluate the secretion of IGF-II.

Results published in the January 23, 2012, online edition of the journal BMC Gastroenterology revealed that luteolin reduced HT-29 cell growth by inducing apoptosis and cell cycle arrest. Senior author Dr. Jung Han Yoon Park, professor of food science and nutrition at Hallym University, explained, “Luteolin reduced IGF-I-dependent activation of the cell signaling pathways PI3K, Akt, and ERK1/2 and CDC25c. Blocking these pathways stops cancer cells from dividing and leads to cell death. Our study, showing that luteolin interferes with cell signaling in colon cancer cells, is a step forward in understanding how this flavonoid works. A fuller understanding of the in vivo results is essential to determine how it might be developed into an effective chemopreventive agent.”

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