Abstract
Altered Notch signaling seems linked with medulloblastoma (MB) formation and resveratrol exhibits anti-medulloblastoma effects. However, the influence of resveratrol in Notch signaling of MB cells has not been described. This issue was addressed here by checking Notch1 and Notch2 statuses in three MB cell lines with and without resveratrol treatment. Notch1 and Notch2 were detected in the cytoplasm of three cell lines under normal condition, which were up-regulated by resveratrol along with differentiation, apoptosis and enhanced Hes1 nuclear translocation. Nevertheless, blockage of Notch enzymatic cleavage with gamma-seacretase inhibitors, DAPT and L-685,458, neither interrupted resveratrol-caused cellular events nor affected MB cell growth. These results demonstrate that Notch signaling has little relevance with resveratrol-induced differentiation and apoptosis and may not be a universal critical factor of MB cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / drug effects
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Active Transport, Cell Nucleus / physiology
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Amyloid Precursor Protein Secretases / antagonists & inhibitors
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Amyloid Precursor Protein Secretases / metabolism
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Antioxidants / pharmacology
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Antioxidants / therapeutic use
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Apoptosis / drug effects
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Apoptosis / physiology
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Basic Helix-Loop-Helix Transcription Factors / drug effects
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Brain Neoplasms / drug therapy
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Brain Neoplasms / metabolism*
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cytoplasm / drug effects
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Cytoplasm / metabolism
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Enzyme Inhibitors / pharmacology
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Homeodomain Proteins / drug effects
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Homeodomain Proteins / metabolism
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Humans
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Medulloblastoma / drug therapy
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Medulloblastoma / metabolism*
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Receptor, Notch1 / drug effects
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Receptor, Notch1 / metabolism
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Receptor, Notch2 / drug effects
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Receptor, Notch2 / metabolism
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Receptors, Notch / metabolism*
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Resveratrol
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Stilbenes / pharmacology*
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Stilbenes / therapeutic use
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Transcription Factor HES-1
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Up-Regulation / drug effects
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Up-Regulation / physiology
Substances
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Antineoplastic Agents
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Antioxidants
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Basic Helix-Loop-Helix Transcription Factors
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Enzyme Inhibitors
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Homeodomain Proteins
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NOTCH1 protein, human
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NOTCH2 protein, human
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Receptor, Notch1
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Receptor, Notch2
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Receptors, Notch
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Stilbenes
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Transcription Factor HES-1
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HES1 protein, human
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Amyloid Precursor Protein Secretases
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Resveratrol