Fucoidan downregulates insulin-like growth factor-I receptor levels in HT-29 human colon cancer cells

  • Authors:
    • In-Hye Kim
    • Taek-Jeong Nam
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  • Published online on: January 4, 2018     https://doi.org/10.3892/or.2018.6193
  • Pages: 1516-1522
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Abstract

Fucoidan, a sulfated polysaccharide present in brown seaweed, has demonstrated anticancer activity in lung, breast, liver and colon cells. The insulin-like growth factor (IGF) signaling pathway regulates growth in HT-29 cells through the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Ras/Raf/extracellular signal-regulated kinase (ERK) pathways. The aim of the present study was to investigate whether fucoidan downregulates the IGF-IR signaling pathway in HT-29 human colon cancer cells. Fucoidan treatment (0-1,000 µg/ml) was administered for 24 h in HT-29 cells. First, we investigated IRS-1/PI3K/AKT pathway-related protein expression levels following treatment with fucoidan (0-500 µg/ml) using western blot analysis. Fucoidan significantly inhibited the expression of IGF-IR, PTEN, PI3K and AKT as well as their phosphorylated forms (p-IRS-1, p-PI3K and p-AKT). Next, we investigated the effects of fucoidan on Ras/Raf/ERK pathway‑related protein expression levels in HT-29 cells. Fucoidan significantly inhibited the expression of IGF-IR, Shc, Ras, SOS, Raf and MEK. HT-29 cells were then incubated in the presence of fucoidan (0 or 250 µg/ml), and IGF-I (10 nM) was added for 0 to 60 min. Immunoprecipitation (IP) experiments showed that fucoidan inhibited IGF-I-induced phosphorylation of IGF-IR, PI3K, Shc (IP, IGF-IR), and phosphorylated IRS-1 and PI3K (IP, IRS-1) compared to the control group. Western blot analysis showed that fucoidan inhibited the expression of IGF-I-induced p-IGF-IR/IGF-IR and p-AKT/AKT, but not p-ERK/ERK. In conclusion, the inhibition of cell viability by fucoidan in HT-29 cells may be due to the downregulation of IGF-IR signaling through the main IRS-1/PI3K/AKT pathway. Fucoidan also partially impacted Ras/Raf signaling in the Ras/Raf/ERK pathway. Therefore, we suggest that fucoidan may be a suitable candidate chemopreventive agent in HT-29 colon cancer cells.
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March-2018
Volume 39 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Kim I and Nam T: Fucoidan downregulates insulin-like growth factor-I receptor levels in HT-29 human colon cancer cells. Oncol Rep 39: 1516-1522, 2018.
APA
Kim, I., & Nam, T. (2018). Fucoidan downregulates insulin-like growth factor-I receptor levels in HT-29 human colon cancer cells. Oncology Reports, 39, 1516-1522. https://doi.org/10.3892/or.2018.6193
MLA
Kim, I., Nam, T."Fucoidan downregulates insulin-like growth factor-I receptor levels in HT-29 human colon cancer cells". Oncology Reports 39.3 (2018): 1516-1522.
Chicago
Kim, I., Nam, T."Fucoidan downregulates insulin-like growth factor-I receptor levels in HT-29 human colon cancer cells". Oncology Reports 39, no. 3 (2018): 1516-1522. https://doi.org/10.3892/or.2018.6193