title: Fucoidan extract induces apoptosis in MCF-7 cells via a mechanism involving the ROS-dependent JNK activation and mitochondria-mediated pathways.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Teruya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Eto
authors.forename: Sanetaka
authors.initials: S
authors.lastname: Shirahata
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D011134:Polysaccharides; D017382:Reactive Oxygen Species; C007789:fucoidan; D048031:JNK Mitogen-Activated Protein Kinases
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