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The effects of fucodian on senescence are controlled by the p16(INK4a)-pRb and p14(Arf)-p53 pathways in hepatocellular carcinoma and hepatic cell lines
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 fu...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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D.A. Spandidos
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079163/ https://www.ncbi.nlm.nih.gov/pubmed/24807532 http://dx.doi.org/10.3892/ijo.2014.2426 |
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author | MIN, EUN-YOUNG KIM, IN-HYE LEE, JUNGIM KIM, EUN-YOUNG CHOI, YOUN-HEE NAM, TAEK-JEONG |
author_facet | MIN, EUN-YOUNG KIM, IN-HYE LEE, JUNGIM KIM, EUN-YOUNG CHOI, YOUN-HEE NAM, TAEK-JEONG |
author_sort | MIN, EUN-YOUNG |
collection | PubMed |
description | 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 G(1) phase arrest was caused by the activity of the p16(INK4a)-Rb and p14(Arf)-p53 pathways. Furthermore, upregulation of p16(INK4a) 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 p14(Arf) expression as cells enter quiescence, with the reduction of p16(INK4a). Fucoidan treatment also downregulated the expression of α(2)M. 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. |
format | Online Article Text |
id | pubmed-4079163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-40791632014-07-02 The effects of fucodian on senescence are controlled by the p16(INK4a)-pRb and p14(Arf)-p53 pathways in hepatocellular carcinoma and hepatic cell lines MIN, EUN-YOUNG KIM, IN-HYE LEE, JUNGIM KIM, EUN-YOUNG CHOI, YOUN-HEE NAM, TAEK-JEONG Int J Oncol Articles 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 G(1) phase arrest was caused by the activity of the p16(INK4a)-Rb and p14(Arf)-p53 pathways. Furthermore, upregulation of p16(INK4a) 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 p14(Arf) expression as cells enter quiescence, with the reduction of p16(INK4a). Fucoidan treatment also downregulated the expression of α(2)M. 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. D.A. Spandidos 2014-05-08 /pmc/articles/PMC4079163/ /pubmed/24807532 http://dx.doi.org/10.3892/ijo.2014.2426 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Articles MIN, EUN-YOUNG KIM, IN-HYE LEE, JUNGIM KIM, EUN-YOUNG CHOI, YOUN-HEE NAM, TAEK-JEONG The effects of fucodian on senescence are controlled by the p16(INK4a)-pRb and p14(Arf)-p53 pathways in hepatocellular carcinoma and hepatic cell lines |
title | The effects of fucodian on senescence are controlled by the p16(INK4a)-pRb and p14(Arf)-p53 pathways in hepatocellular carcinoma and hepatic cell lines |
title_full | The effects of fucodian on senescence are controlled by the p16(INK4a)-pRb and p14(Arf)-p53 pathways in hepatocellular carcinoma and hepatic cell lines |
title_fullStr | The effects of fucodian on senescence are controlled by the p16(INK4a)-pRb and p14(Arf)-p53 pathways in hepatocellular carcinoma and hepatic cell lines |
title_full_unstemmed | The effects of fucodian on senescence are controlled by the p16(INK4a)-pRb and p14(Arf)-p53 pathways in hepatocellular carcinoma and hepatic cell lines |
title_short | The effects of fucodian on senescence are controlled by the p16(INK4a)-pRb and p14(Arf)-p53 pathways in hepatocellular carcinoma and hepatic cell lines |
title_sort | effects of fucodian on senescence are controlled by the p16(ink4a)-prb and p14(arf)-p53 pathways in hepatocellular carcinoma and hepatic cell lines |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079163/ https://www.ncbi.nlm.nih.gov/pubmed/24807532 http://dx.doi.org/10.3892/ijo.2014.2426 |
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