Open Access

The effects of fucodian on senescence are controlled by the p16INK4a-pRb and p14Arf-p53 pathways in hepatocellular carcinoma and hepatic cell lines

  • Authors:
    • Eun-Young Min
    • In-Hye Kim
    • Jungim Lee
    • Eun-Young Kim
    • Youn-Hee Choi
    • Taek-Jeong Nam
  • View Affiliations

  • Published online on: May 8, 2014     https://doi.org/10.3892/ijo.2014.2426
  • Pages: 47-56
  • Copyright: © Min et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Fucoidan is known to have various pharmacological effects, including antitumor activity. Although it has potential as a therapeutic agent for cancer cells, the anti-senescence effects and detailed mechanism of action remain poorly understood in normal hepatic cells. We investigated the anticancer functions of fucoidan using HepG2 cells as well as the mechanisms mediating the anti-senescent actions in Chang liver cells. Fucoidan effectively inhibited HepG2 cell viability and induced apoptosis. Also, fucoidan-induced G1 phase arrest was caused by the activity of the p16INK4a-Rb and p14Arf-p53 pathways. Furthermore, upregulation of p16INK4a was critical to the antitumor activity of HepG2 cells treated with fucoidan and was correlated with inhibition of Cdk4 and pRb and upregulation of p21 expression. Our results suggest that fucoidan upregulates INK4a locus genes to induce apoptosis through p38 MAPK in HepG2 cells. Moreover, it prevents cellular senescence of Chang-L cells, by decreasing p14Arf expression as cells enter quiescence, with the reduction of p16INK4a. Fucoidan treatment also downregulated the expression of α2M. In conclusion, fucoidan can be considered a potential therapeutic agent against liver cancer that does not cause senescence in normal hepatic cells. Thus, it may be possible to use fucoidan therapeutically in both tumor suppression and aging.
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July-2014
Volume 45 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Min E, Kim I, Lee J, Kim E, Choi Y and Nam T: The effects of fucodian on senescence are controlled by the p16INK4a-pRb and p14Arf-p53 pathways in hepatocellular carcinoma and hepatic cell lines. Int J Oncol 45: 47-56, 2014
APA
Min, E., Kim, I., Lee, J., Kim, E., Choi, Y., & Nam, T. (2014). The effects of fucodian on senescence are controlled by the p16INK4a-pRb and p14Arf-p53 pathways in hepatocellular carcinoma and hepatic cell lines. International Journal of Oncology, 45, 47-56. https://doi.org/10.3892/ijo.2014.2426
MLA
Min, E., Kim, I., Lee, J., Kim, E., Choi, Y., Nam, T."The effects of fucodian on senescence are controlled by the p16INK4a-pRb and p14Arf-p53 pathways in hepatocellular carcinoma and hepatic cell lines". International Journal of Oncology 45.1 (2014): 47-56.
Chicago
Min, E., Kim, I., Lee, J., Kim, E., Choi, Y., Nam, T."The effects of fucodian on senescence are controlled by the p16INK4a-pRb and p14Arf-p53 pathways in hepatocellular carcinoma and hepatic cell lines". International Journal of Oncology 45, no. 1 (2014): 47-56. https://doi.org/10.3892/ijo.2014.2426