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Published on: December 25, 2021
Selective targeting of the DEAD-box RNA helicase eukaryotic initiation factor (eIF) 4A by natural products
1Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada. jerry.pelletier@mcgill.ca.
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.
Insights
Natural products like hippuristanol, rocaglates, and pateamine A target eukaryotic initiation factor 4A (eIF4A) to inhibit cancer cell growth. These compounds selectively alter gene expression, showing potent anti-tumorigenic effects in preclinical studies.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Targeting mRNA translation initiation is a key strategy in cancer therapy due to its deregulation in tumors.
- Eukaryotic initiation factor 4A (eIF4A), a DEAD-box helicase, is crucial for translation initiation and 43S pre-initiation complex loading onto mRNAs.
Purpose of the Study:
- To review the molecular mechanisms of action of natural products that target eIF4A.
- To update on the anti-tumorigenic activities of hippuristanol, rocaglates, and pateamine A.
Main Methods:
- Literature review of studies up to 2019.
- Analysis of molecular mechanisms of natural product interaction with eIF4A.
- Review of preclinical anti-tumorigenic activity data.
Main Results:
- Hippuristanol, rocaglates, and pateamine A inhibit eIF4A by distinct mechanisms affecting its RNA-binding activity.
- These natural products induce selective changes in gene expression.
- Potent anti-tumorigenic activity observed in preclinical studies.
Conclusions:
- Natural products targeting eIF4A offer a promising pharmacological approach for cancer therapy.
- Understanding their distinct mechanisms can guide the development of novel anti-cancer drugs.
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