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

doi:10.1371/journal.pone.0027441

Cited by 167Seaweed-derived Bioactive CompoundsCell death mechanisms and regulationNatural product bioactivities and synthesis

Fucoidan extract induces apoptosis in MCF-7 cells via a mechanism involving the ROS-dependent JNK activation and mitochondria-mediated pathways

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Zhang, Zhongyuan, Teruya, Kiichiro, Eto, Hiroshi, Shirahata, Sanetaka·2011·PLoS ONE

DOI 10.1371/journal.pone.0027441PMC PMC3214060

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Abstract

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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The caspase-independent apoptotic pathway was demonstrated for fucoidan from Cladosiphon novae-caledoniae.
“The caspase-independent apoptotic pathway was demonstrated for fucoidan from Cladosiphon novae-caledoniae [41].”
From Anticancer and Cancer Preventive Properties of Marine Polysaccharides: Some Results and Prospects (2013) · cites this paper as [41]
Sometimes this mechanism involved ROS-dependent JNK activation, as shown for partly digested fucoidan from C. novae-caledoniae using MCF-7 and MDA-MB-10A tumor cells.
“Sometimes this mechanism involved the reactive oxygen species (ROS)-dependent JNK activation as was shown for partly digested fucoidan from commercially available seaweed C. novae-caledoniae using MCF-7 and MDA-MB-10A tumor cells [41].”
From Anticancer and Cancer Preventive Properties of Marine Polysaccharides: Some Results and Prospects (2013) · cites this paper as [41]

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Alginate–polyester comacromer based hydrogels as physiochemically and biologically favorable entities for cardiac tissue engineering
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Authors: Zhang, Z., Teruya, K., Eto, H., & Shirahata, S.
Affiliations: Kyushu University (JP)
Daiichi-Sankyo (Japan) (JP)
Corresponding author: Teruya, Kiichiro
ORCID: Zhang, Zhongyuan
Teruya, Kiichiro
Shirahata, Sanetaka
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2011-11-11
Volume: 6
Issue: 11
Pages: e27441
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0027441
PMC: PMC3214060
OpenAlex: W2129739698
Cited by: 167
References: 59
Citations by year: 2026: 5 · 2025: 8 · 2024: 8 · 2023: 14 · 2022: 12 · 2021: 10 · 2020: 9 · 2019: 15 · 2018: 13 · 2017: 10 · 2016: 12 · 2015: 13 · 2014: 16 · 2013: 14 · 2012: 8
FWCI: 18.42
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Japan Society for the Promotion of Science (23580172)
Topics: Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Seaweed-derived Bioactive Compounds
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
Keywords: fucoidan, apoptosis, MCF-7 cells, breast cancer, reactive oxygen species, JNK activation, MAPK signaling, mitochondrial membrane permeabilization, mitochondrial membrane potential, Bcl-2 family proteins, apoptosis-inducing factor, cytochrome c release, caspase-independent apoptosis, p38 MAPK, ERK1/2, anticancer natural compounds, brown seaweed extract
MeSH terms: Enzyme Activation, Humans, Mitochondria, Polysaccharides, Signal Transduction, Apoptosis, Reactive Oxygen Species, Cell Line, Tumor, JNK Mitogen-Activated Protein Kinases

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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

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