Fucoidan Induces Apoptosis of HT-29 Cells via the Activation of DR4 and Mitochondrial Pathway

Fucoidan has a variety of pharmacological activities, but the understanding of the mechanism of fucoidan-induced apoptosis of colorectal cancer cells remains limited. The results of the present study demonstrated that the JNK signaling pathway is involved in the activation of apoptosis in colorectal...

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Main Authors: Xu Bai, Yu Wang, Bo Hu, Qi Cao, Maochen Xing, Shuliang Song, Aiguo Ji
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/18/4/220
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author Xu Bai
Yu Wang
Bo Hu
Qi Cao
Maochen Xing
Shuliang Song
Aiguo Ji
author_facet Xu Bai
Yu Wang
Bo Hu
Qi Cao
Maochen Xing
Shuliang Song
Aiguo Ji
author_sort Xu Bai
collection DOAJ
description Fucoidan has a variety of pharmacological activities, but the understanding of the mechanism of fucoidan-induced apoptosis of colorectal cancer cells remains limited. The results of the present study demonstrated that the JNK signaling pathway is involved in the activation of apoptosis in colorectal cancer-derived HT-29 cells, and fucoidan induces apoptosis by activation of the DR4 at the transcriptional and protein levels. The survival rate of HT-29 cells was approximately 40% in the presence of 800 μg/mL of fucoidan, but was increased to 70% after DR4 was silenced by siRNA. Additionally, fucoidan has been shown to reduce the mitochondrial membrane potential and destroy the integrity of mitochondrial membrane. In the presence of an inhibitor of cytochrome C inhibitor and DR4 siRNA or the presence of cytochrome C inhibitor only, the cell survival rate was significantly higher than when cells were treated with DR4 siRNA only. These data indicate that both the DR4 and the mitochondrial pathways contribute to fucoidan-induced apoptosis of HT-29 cells, and the extrinsic pathway is upstream of the intrinsic pathway. In conclusion, the current work identified the mechanism of fucoidan-induced apoptosis and provided a novel theoretical basis for the future development of clinical applications of fucoidan as a drug.
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spelling doaj.art-7b54736a2bae40f384c311092f2e4a2c2023-11-19T22:11:55ZengMDPI AGMarine Drugs1660-33972020-04-0118422010.3390/md18040220Fucoidan Induces Apoptosis of HT-29 Cells via the Activation of DR4 and Mitochondrial PathwayXu Bai0Yu Wang1Bo Hu2Qi Cao3Maochen Xing4Shuliang Song5Aiguo Ji6Marine College, Shandong University, Weihai 264209, ChinaMarine College, Shandong University, Weihai 264209, ChinaMarine College, Shandong University, Weihai 264209, ChinaMarine College, Shandong University, Weihai 264209, ChinaMarine College, Shandong University, Weihai 264209, ChinaMarine College, Shandong University, Weihai 264209, ChinaMarine College, Shandong University, Weihai 264209, ChinaFucoidan has a variety of pharmacological activities, but the understanding of the mechanism of fucoidan-induced apoptosis of colorectal cancer cells remains limited. The results of the present study demonstrated that the JNK signaling pathway is involved in the activation of apoptosis in colorectal cancer-derived HT-29 cells, and fucoidan induces apoptosis by activation of the DR4 at the transcriptional and protein levels. The survival rate of HT-29 cells was approximately 40% in the presence of 800 μg/mL of fucoidan, but was increased to 70% after DR4 was silenced by siRNA. Additionally, fucoidan has been shown to reduce the mitochondrial membrane potential and destroy the integrity of mitochondrial membrane. In the presence of an inhibitor of cytochrome C inhibitor and DR4 siRNA or the presence of cytochrome C inhibitor only, the cell survival rate was significantly higher than when cells were treated with DR4 siRNA only. These data indicate that both the DR4 and the mitochondrial pathways contribute to fucoidan-induced apoptosis of HT-29 cells, and the extrinsic pathway is upstream of the intrinsic pathway. In conclusion, the current work identified the mechanism of fucoidan-induced apoptosis and provided a novel theoretical basis for the future development of clinical applications of fucoidan as a drug.https://www.mdpi.com/1660-3397/18/4/220fucoidanapoptosisDR4mitochondrial pathway
spellingShingle Xu Bai
Yu Wang
Bo Hu
Qi Cao
Maochen Xing
Shuliang Song
Aiguo Ji
Fucoidan Induces Apoptosis of HT-29 Cells via the Activation of DR4 and Mitochondrial Pathway
Marine Drugs
fucoidan
apoptosis
DR4
mitochondrial pathway
title Fucoidan Induces Apoptosis of HT-29 Cells via the Activation of DR4 and Mitochondrial Pathway
title_full Fucoidan Induces Apoptosis of HT-29 Cells via the Activation of DR4 and Mitochondrial Pathway
title_fullStr Fucoidan Induces Apoptosis of HT-29 Cells via the Activation of DR4 and Mitochondrial Pathway
title_full_unstemmed Fucoidan Induces Apoptosis of HT-29 Cells via the Activation of DR4 and Mitochondrial Pathway
title_short Fucoidan Induces Apoptosis of HT-29 Cells via the Activation of DR4 and Mitochondrial Pathway
title_sort fucoidan induces apoptosis of ht 29 cells via the activation of dr4 and mitochondrial pathway
topic fucoidan
apoptosis
DR4
mitochondrial pathway
url https://www.mdpi.com/1660-3397/18/4/220
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