Abstract
Covering: up to 2019Pharmacological targeting of eukaryotic mRNA translation initiation is a promising approach for cancer therapy, since several signaling pathways that are commonly deregulated during tumor progression converge on this process. The DEAD-box helicase, eukaryotic initiation factor (eIF) 4A, is essential for translation initiation and facilitates the loading of the 43S pre-initiation complex onto mRNAs. Hippuristanol, rocaglates, and pateamine A are natural products that each target eIF4A by interfering with the helicase's RNA-binding activity in distinct manners. They exert a selective change in gene expression that results in potent anti-tumorigenic activity in pre-clinical studies. This review will provide an update on the molecular mechanisms of action of these natural products.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology*
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Biological Products / chemistry
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Biological Products / pharmacology*
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DEAD-box RNA Helicases / antagonists & inhibitors
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DEAD-box RNA Helicases / metabolism
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Epoxy Compounds / pharmacology
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Eukaryotic Initiation Factor-4A / antagonists & inhibitors
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Eukaryotic Initiation Factor-4A / metabolism*
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Gene Expression Regulation / drug effects
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Humans
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Macrolides / pharmacology
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Molecular Targeted Therapy
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Neoplasms / drug therapy
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Protein Biosynthesis / drug effects
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Protein Biosynthesis / physiology
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Sterols / pharmacology
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Thiazoles / pharmacology
Substances
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Antineoplastic Agents
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Biological Products
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Epoxy Compounds
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Macrolides
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Sterols
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Thiazoles
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hippuristanol
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pateamine A
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Eukaryotic Initiation Factor-4A
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DEAD-box RNA Helicases