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Fucoidan Extract Induces Apoptosis in MCF-7 Cells via a Mechanism Involving the ROS-Dependent JNK Activation and Mitochondria-Mediated Pathways

BACKGROUND: Fucoidan extract (FE), an enzymatically digested compound with a low molecular weight, is extracted from brown seaweed. As a natural compound with various actions, FE is attractive, especially in Asian countries, for improving the therapeutic efficacy and safety of cancer treatment. The...

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Autores principales: Zhang, Zhongyuan, Teruya, Kiichiro, Eto, Hiroshi, Shirahata, Sanetaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214060/
https://www.ncbi.nlm.nih.gov/pubmed/22096572
http://dx.doi.org/10.1371/journal.pone.0027441
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author Zhang, Zhongyuan
Teruya, Kiichiro
Eto, Hiroshi
Shirahata, Sanetaka
author_facet Zhang, Zhongyuan
Teruya, Kiichiro
Eto, Hiroshi
Shirahata, Sanetaka
author_sort Zhang, Zhongyuan
collection PubMed
description BACKGROUND: Fucoidan extract (FE), an enzymatically digested compound with a low molecular weight, is extracted from brown seaweed. As a natural compound with various actions, FE is attractive, especially in Asian countries, for improving the therapeutic efficacy and safety of cancer treatment. The present study was carried out to investigate the anti-tumor properties of FE in human carcinoma cells and further examine the underlying mechanisms of its activities. METHODOLOGY/PRINCIPAL FINDING: FE inhibits the growth of MCF-7, MDA-MB-231, HeLa, and HT1080 cells. FE-mediated apoptosis in MCF-7 cancer cells is accompanied by DNA fragmentation, nuclear condensation, and phosphatidylserine exposure. FE induces mitochondrial membrane permeabilization (MMP) through loss of mitochondrial membrane potential (ΔΨm) and regulation of the expression of Bcl-2 family members. Release of apoptosis-inducing factor (AIF) and cytochrome c precedes MMP. AIF release causes DNA fragmentation, the final stage of apoptosis, via a caspase-independent mitochondrial pathway. Additionally, FE was found to induce phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) 1/2, and apoptosis was found to be attenuated by inhibition of JNK. Furthermore, FE-mediated apoptosis was found to involve the generation of reactive oxygen species (ROS), which are responsible for the decrease of ΔΨm and phosphorylation of JNK, p38, and ERK1/2 kinases. CONCLUSIONS/SIGNIFICANCE: These data suggest that FE activates a caspase-independent apoptotic pathway in MCF-7 cancer cells through activation of ROS-mediated MAP kinases and regulation of the Bcl-2 family protein-mediated mitochondrial pathway. They also provide evidence that FE deserves further investigation as a natural anticancer and cancer preventive agent.
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spelling pubmed-32140602011-11-17 Fucoidan Extract Induces Apoptosis in MCF-7 Cells via a Mechanism Involving the ROS-Dependent JNK Activation and Mitochondria-Mediated Pathways Zhang, Zhongyuan Teruya, Kiichiro Eto, Hiroshi Shirahata, Sanetaka PLoS One Research Article BACKGROUND: Fucoidan extract (FE), an enzymatically digested compound with a low molecular weight, is extracted from brown seaweed. As a natural compound with various actions, FE is attractive, especially in Asian countries, for improving the therapeutic efficacy and safety of cancer treatment. The present study was carried out to investigate the anti-tumor properties of FE in human carcinoma cells and further examine the underlying mechanisms of its activities. METHODOLOGY/PRINCIPAL FINDING: FE inhibits the growth of MCF-7, MDA-MB-231, HeLa, and HT1080 cells. FE-mediated apoptosis in MCF-7 cancer cells is accompanied by DNA fragmentation, nuclear condensation, and phosphatidylserine exposure. FE induces mitochondrial membrane permeabilization (MMP) through loss of mitochondrial membrane potential (ΔΨm) and regulation of the expression of Bcl-2 family members. Release of apoptosis-inducing factor (AIF) and cytochrome c precedes MMP. AIF release causes DNA fragmentation, the final stage of apoptosis, via a caspase-independent mitochondrial pathway. Additionally, FE was found to induce phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) 1/2, and apoptosis was found to be attenuated by inhibition of JNK. Furthermore, FE-mediated apoptosis was found to involve the generation of reactive oxygen species (ROS), which are responsible for the decrease of ΔΨm and phosphorylation of JNK, p38, and ERK1/2 kinases. CONCLUSIONS/SIGNIFICANCE: These data suggest that FE activates a caspase-independent apoptotic pathway in MCF-7 cancer cells through activation of ROS-mediated MAP kinases and regulation of the Bcl-2 family protein-mediated mitochondrial pathway. They also provide evidence that FE deserves further investigation as a natural anticancer and cancer preventive agent. Public Library of Science 2011-11-11 /pmc/articles/PMC3214060/ /pubmed/22096572 http://dx.doi.org/10.1371/journal.pone.0027441 Text en Zhang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhang, Zhongyuan
Teruya, Kiichiro
Eto, Hiroshi
Shirahata, Sanetaka
Fucoidan Extract Induces Apoptosis in MCF-7 Cells via a Mechanism Involving the ROS-Dependent JNK Activation and Mitochondria-Mediated Pathways
title Fucoidan Extract Induces Apoptosis in MCF-7 Cells via a Mechanism Involving the ROS-Dependent JNK Activation and Mitochondria-Mediated Pathways
title_full Fucoidan Extract Induces Apoptosis in MCF-7 Cells via a Mechanism Involving the ROS-Dependent JNK Activation and Mitochondria-Mediated Pathways
title_fullStr Fucoidan Extract Induces Apoptosis in MCF-7 Cells via a Mechanism Involving the ROS-Dependent JNK Activation and Mitochondria-Mediated Pathways
title_full_unstemmed Fucoidan Extract Induces Apoptosis in MCF-7 Cells via a Mechanism Involving the ROS-Dependent JNK Activation and Mitochondria-Mediated Pathways
title_short Fucoidan Extract Induces Apoptosis in MCF-7 Cells via a Mechanism Involving the ROS-Dependent JNK Activation and Mitochondria-Mediated Pathways
title_sort fucoidan extract induces apoptosis in mcf-7 cells via a mechanism involving the ros-dependent jnk activation and mitochondria-mediated pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214060/
https://www.ncbi.nlm.nih.gov/pubmed/22096572
http://dx.doi.org/10.1371/journal.pone.0027441
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