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

Authors :
Hye Young Park
Shin-Hyung Park
Jin-Woo Jeong
Dahye Yoon
Min Ho Han
Dae-Sung Lee
Grace Choi
Mi-Jin Yim
Jeong Min Lee
Do-Hyung Kim
Gi-Young Kim
Il-Whan Choi
Suhkmann Kim
Heui-Soo Kim
Hee-Jae Cha
Yung Hyun Choi
Source :
Marine Drugs, Vol 15, Iss 6, p 154 (2017)
Publication Year :
2017
Publisher :
MDPI AG, 2017.

Abstract

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.

Details

Language :
English
ISSN :
16603397
Volume :
15
Issue :
6
Database :
Directory of Open Access Journals
Journal :
Marine Drugs
Publication Type :
Academic Journal
Accession number :
edsdoj.5528bc32066b4b0e82ee30a8690143b3
Document Type :
article
Full Text :
https://doi.org/10.3390/md15060154