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

Hye Park,Mi-Jin Yim,Grace Choi,Dae-Sung Lee,Suhkmann Kim,Gi-Young Kim,Heui-Soo Kim,Jeong Lee,Min Han,Jin-Woo Jeong,Hee-Jae Cha,Dahye Yoon,Shin-Hyung Park,Do-Hyung Kim,Il-Whan Choi,Yung Choi

doi:10.3390/md15060154

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.

Highlights

Colorectal cancer (CRC) is one of the most common cancers worldwide
We found that fucoidan triggered apoptosis and G1 cell cycle arrest in wild-type p53 (p53+/+) HCT116 cells and in p53 allele-null (p53−/−) HCT116 cells, suggesting that fucoidan could be a possible therapeutic option for CRC regardless of its p53 status
[25], we examined the effect of fucoidan on thethe is fragmented by the activated caspase cascade [25], we examined the effect of fucoidan on expression of to provide further support for the hypothesis that fucoidan‐induced apoptosis expression of PARP to provide further support for the hypothesis that fucoidan-induced apoptosis in in HCT116 cells

Summary

Introduction

Colorectal cancer (CRC) is one of the most common cancers worldwide. It accounts for about10% of all cancer cases, making it the third most common cancer. Colorectal cancer (CRC) is one of the most common cancers worldwide. 10% of all cancer cases, making it the third most common cancer. CRC is the fourth leading cause of cancer-related death, with more than 700,000 people dying from CRC every year [1,2,3]. Most cases of CRC are detected in Western countries, its incidence has rapidly increased in. East Asia and Eastern Europe over the past few years due to the dietary shift toward a more “Western diet” characterized by a large amount of red meat and fat [4,5]. There is a need to develop novel therapeutic strategies for CRC [6]

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