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Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells

It is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here, we investi...

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Autores principales: Park, Hye Young, Park, Shin-Hyung, Jeong, Jin-Woo, Yoon, Dahye, Han, Min Ho, Lee, Dae-Sung, Choi, Grace, Yim, Mi-Jin, Lee, Jeong Min, Kim, Do-Hyung, Kim, Gi-Young, Choi, Il-Whan, Kim, Suhkmann, Kim, Heui-Soo, Cha, Hee-Jae, Choi, Yung Hyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484104/
https://www.ncbi.nlm.nih.gov/pubmed/28555064
http://dx.doi.org/10.3390/md15060154
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author Park, Hye Young
Park, Shin-Hyung
Jeong, Jin-Woo
Yoon, Dahye
Han, Min Ho
Lee, Dae-Sung
Choi, Grace
Yim, Mi-Jin
Lee, Jeong Min
Kim, Do-Hyung
Kim, Gi-Young
Choi, Il-Whan
Kim, Suhkmann
Kim, Heui-Soo
Cha, Hee-Jae
Choi, Yung Hyun
author_facet Park, Hye Young
Park, Shin-Hyung
Jeong, Jin-Woo
Yoon, Dahye
Han, Min Ho
Lee, Dae-Sung
Choi, Grace
Yim, Mi-Jin
Lee, Jeong Min
Kim, Do-Hyung
Kim, Gi-Young
Choi, Il-Whan
Kim, Suhkmann
Kim, Heui-Soo
Cha, Hee-Jae
Choi, Yung Hyun
author_sort Park, Hye Young
collection PubMed
description It is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here, we investigated the anticancer effect of fucoidan on two p53 isogenic HCT116 (p53+/+ and p53−/−) cell lines. Our results showed that inhibition of cell viability, induction of apoptosis and DNA damage by treatment with fucoidan were similar in two cell lines. Flow cytometric analysis revealed that fucoidan resulted in G1 arrest in the cell cycle progression, which correlated with the inhibition of phosphorylation of retinoblastoma protein (pRB) and concomitant association of pRB with the transcription factor E2Fs. Furthermore, treatment with fucoidan obviously upregulated the expression of cyclin-dependent kinase (CDK) inhibitors, such as p21WAF1/CIP1 and p27KIP1, which was paralleled by an enhanced binding with CDK2 and CDK4. These events also commonly occurred in both cell lines, suggesting that fucoidan triggered G1 arrest and apoptosis in HCT116 cells by a p53-independent mechanism. Thus, given that most tumors exhibit functional p53 inactivation, fucoidan could be a possible therapeutic option for cancer treatment regardless of the p53 status.
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spelling pubmed-54841042017-06-29 Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells Park, Hye Young Park, Shin-Hyung Jeong, Jin-Woo Yoon, Dahye Han, Min Ho Lee, Dae-Sung Choi, Grace Yim, Mi-Jin Lee, Jeong Min Kim, Do-Hyung Kim, Gi-Young Choi, Il-Whan Kim, Suhkmann Kim, Heui-Soo Cha, Hee-Jae Choi, Yung Hyun Mar Drugs Article It is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here, we investigated the anticancer effect of fucoidan on two p53 isogenic HCT116 (p53+/+ and p53−/−) cell lines. Our results showed that inhibition of cell viability, induction of apoptosis and DNA damage by treatment with fucoidan were similar in two cell lines. Flow cytometric analysis revealed that fucoidan resulted in G1 arrest in the cell cycle progression, which correlated with the inhibition of phosphorylation of retinoblastoma protein (pRB) and concomitant association of pRB with the transcription factor E2Fs. Furthermore, treatment with fucoidan obviously upregulated the expression of cyclin-dependent kinase (CDK) inhibitors, such as p21WAF1/CIP1 and p27KIP1, which was paralleled by an enhanced binding with CDK2 and CDK4. These events also commonly occurred in both cell lines, suggesting that fucoidan triggered G1 arrest and apoptosis in HCT116 cells by a p53-independent mechanism. Thus, given that most tumors exhibit functional p53 inactivation, fucoidan could be a possible therapeutic option for cancer treatment regardless of the p53 status. MDPI 2017-05-30 /pmc/articles/PMC5484104/ /pubmed/28555064 http://dx.doi.org/10.3390/md15060154 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Park, Hye Young
Park, Shin-Hyung
Jeong, Jin-Woo
Yoon, Dahye
Han, Min Ho
Lee, Dae-Sung
Choi, Grace
Yim, Mi-Jin
Lee, Jeong Min
Kim, Do-Hyung
Kim, Gi-Young
Choi, Il-Whan
Kim, Suhkmann
Kim, Heui-Soo
Cha, Hee-Jae
Choi, Yung Hyun
Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells
title Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells
title_full Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells
title_fullStr Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells
title_full_unstemmed Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells
title_short Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells
title_sort induction of p53-independent apoptosis and g1 cell cycle arrest by fucoidan in hct116 human colorectal carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484104/
https://www.ncbi.nlm.nih.gov/pubmed/28555064
http://dx.doi.org/10.3390/md15060154
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