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Blueberry inhibits invasion and angiogenesis in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral squamous cell carcinogenesis in hamsters via suppression of TGF-β and NF-κB signaling pathways
Published in Elsevier Inc.
2016
PMID: 27371785
Volume: 35
   
Pages: 37 - 47
Abstract
Aberrant activation of oncogenic signaling pathways plays a pivotal role in tumor initiation and progression. The purpose of the present study was to investigate the chemopreventive and therapeutic efficacy of blueberry in the hamster buccal pouch (HBP) carcinogenesis model based on its ability to target TGF-β, PI3K/Akt, MAPK and NF-κB signaling and its impact on invasion and angiogenesis. Squamous cell carcinomas were induced in the HBP by 7,12-dimethylbenz[a]anthracene (DMBA). The effect of blueberry on the oncogenic signaling pathways and downstream events was analyzed by quantitative real-time PCR and immunoblotting. Experiments with the ECV304 cell line were performed to explore the mechanism by which blueberry regulates angiogenesis. Blueberry supplementation inhibited the development and progression of HBP carcinomas by abrogating TGF-β and PI3K/Akt pathways. Although blueberry failed to influence MAPK, it suppressed NF-κB activation by preventing nuclear translocation of NF-κB p65. Blueberry also modulated the expression of the oncomiR miR-21 and the tumor suppressor let-7. Collectively, these changes induced a shift to an anti-invasive and anti-angiogenic phenotype as evidenced by downregulating matrix metalloproteinases and vascular endothelial growth factor. Blueberry also inhibited angiogenesis in ECV304 cells by suppressing migration and tube formation. The results of the present study suggest that targeting oncogenic signaling pathways that influence acquisition of cancer hallmarks is an effective strategy for chemointervention. Identification of modulatory effects on phosphorylation, intracellular localization of oncogenic transcription factors and microRNAs unraveled by the present study as key mechanisms of action of blueberry is critical from a therapeutic perspective. © 2016 Elsevier Inc.
About the journal
JournalData powered by TypesetJournal of Nutritional Biochemistry
PublisherData powered by TypesetElsevier Inc.
ISSN09552863
Open AccessNo
Concepts (85)
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    7,12 DIMETHYLBENZ[A]ANTHRACENE
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    Immunoglobulin enhancer binding protein
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    Matrix metalloproteinase
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    MICRORNA 21
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    Mitogen activated protein kinase
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    PHOSPHATIDYLINOSITOL 3 KINASE
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    Protein kinase b
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    TRANSFORMING GROWTH FACTOR BETA
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    VASCULOTROPIN
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    7,12-DIMETHYLBENZ(A)ANTHRACENE
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    BENZ[A]ANTHRACENE DERIVATIVE
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    Carcinogen
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    RELA PROTEIN, RAT
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    TRANSCRIPTION FACTOR RELA
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    TRANSFORMING GROWTH FACTOR BETA
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    Tumor protein
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    Angiogenesis
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    Animal cell
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    Animal experiment
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    Animal model
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    Article
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    BLUEBERRY
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    CARCINOGENESIS
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    Cell migration
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    Cell proliferation
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    Cell viability
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    CHEEK POUCH
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    CHEMOPROPHYLAXIS
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    Controlled study
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    Enzyme activation
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    Enzyme phosphorylation
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    Gene expression
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    IMMUNOBLOTTING
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    Male
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    MOUTH SQUAMOUS CELL CARCINOMA
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    Nonhuman
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    Phenotype
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    Real time polymerase chain reaction
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    SUPPLEMENTATION
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    SYRIAN HAMSTER
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    Tumor invasion
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    Animal
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    Antagonists and inhibitors
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    Chemically induced
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    Chemistry
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    Comparative study
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    DIETARY SUPPLEMENT
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    Drug effects
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    FREEZE DRYING
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    FRUIT
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    Gene expression regulation
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    Genetics
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    Human
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    MESOCRICETUS
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    Metabolism
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    MOUTH NEOPLASMS
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    NEOPLASMS, SQUAMOUS CELL
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    NEOVASCULARIZATION, PATHOLOGIC
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    Nucleocytoplasmic transport
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    Pathology
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    Randomization
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    Signal transduction
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    TRANSFORMED CELL LINE
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    VACCINIUM
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    VASCULARIZATION
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    ACTIVE TRANSPORT, CELL NUCLEUS
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    Animals
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    Benz(a)anthracenes
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    BLUEBERRY PLANTS
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    CARCINOGENS
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    CELL LINE, TRANSFORMED
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    Dietary supplements
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    FREEZE DRYING
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    FRUIT
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    GENE EXPRESSION REGULATION, NEOPLASTIC
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    Humans
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    MESOCRICETUS
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    MOUTH NEOPLASMS
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    Neoplasm invasiveness
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    Neoplasm proteins
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    NEOPLASMS, SQUAMOUS CELL
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    NEOVASCULARIZATION, PATHOLOGIC
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    RANDOM ALLOCATION
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    TRANSCRIPTION FACTOR RELA
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    TRANSFORMING GROWTH FACTOR BETA