title: A Fucus vesiculosus extract inhibits estrogen receptor activation and induces cell death in female cancer cell lines.
abstract: BACKGROUND
  We previously reported the anti-estrogenic activity of the brown seaweed, Fucus vesiculosus. The present study aimed to further investigate its anti-estrogenic modes of action and to assess other potentially biologically relevant anti-tumorigenic effects in estrogen receptor (ER)-dependent and -independent female cancer cell lines.
  
  
  METHODS
  The CALUX® assay was used to determine the effect of a F. vesiculosus extract (FVE) on activation of the ER. Aromatase enzymatic activity was measured to determine the potential effect of FVE on estradiol (E2) biosynthesis. Transcriptional activity profiling of 248 genes involved in cancer, immunity, hormonal regulation, protein phosphorylation, transcription, metabolism, and cellular structure was conducted using the NanoString nCounter® analysis system in FVE-treated breast, ovarian and endometrial cancer cell lines. The effects of FVE on cell viability, morphology, membrane integrity, mitochondrial toxicity, induction of apoptotic and autophagic markers, and cell signaling were also analyzed.
  
  
  RESULTS
  In co-treatments with 12.5 pM (EC50) E2, FVE (2 %) reduced ER activation by 50 %, exhibiting potent ER antagonistic effects. FVE inhibited aromatase activity in an in vitro assay (IC50 2.0 %). ER-dependent and -independent cancer cell lines showed significantly decreased viability that correlated with increasing FVE concentrations and altered morphological features suggestive of apoptosis and autophagy. Expression of genes that were significantly altered by FVE (p < 0.05) revealed predominantly apoptotic, autophagic and kinase signaling pathways. FVE also effectively inhibited the phosphorylation of Akt, resulting in reduced mTORC1 activities to stimulate autophagy in cells. Concentration-dependent cleavage of PARP and induction of caspase-3 and -7 activities were observed in MDA-MB-231 cells supporting a role for FVE in the promotion of apoptosis.
  
  
  CONCLUSIONS
  Our study provides new insights into the anti-estrogenic activity of F. vesiculosus. Moreover, the induction of autophagy and apoptosis on breast, endometrial and ovarian cancer cell lines suggests additional anti-tumorigenic actions of FVE that are independent of ER status in female cancers.
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL, 35294, USA.|The UAB Comprehensive Cancer Center, University of Alabama at Birmingham, 1824 6th Avenue South, Birmingham, 35233, AL, USA.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL, 35294, USA.|The UAB Comprehensive Cancer Center, University of Alabama at Birmingham, 1824 6th Avenue South, Birmingham, 35233, AL, USA.
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Riby
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL, 35294, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Conde
authors.affiliation: Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, 35294, AL, USA.|The UAB Comprehensive Cancer Center, University of Alabama at Birmingham, 1824 6th Avenue South, Birmingham, 35233, AL, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham School of Medicine, Birmingham, 35294, AL, USA.
authors.forename: Xiangqin
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL, 35294, USA. cskibola@uab.edu.|The UAB Comprehensive Cancer Center, University of Alabama at Birmingham, 1824 6th Avenue South, Birmingham, 35233, AL, USA. cskibola@uab.edu.
authors.forename: Christine F
authors.initials: CF
authors.lastname: Skibola
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001141:Aromatase / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D044645:Fucus / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D011960:Receptors, Estrogen; D001141:Aromatase; D020169:Caspases
keywords: Anti-estrogenic activity; Apoptosis; Autophagy; Fucoidan; PI3K signaling; Seaweed