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Synergistic drug combination GC7/DFMO suppresses hypusine/spermidine-dependent eIF5A activation and induces apoptotic cell death in neuroblastoma.

Author: BachmannAndré S, El-KhawajaRaid, GeertsDirk, KosterJan, MooneyMarie, SchultzChad R

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Overview

eIF5A is a protein involved in protein translation that requires a unique hypusine modification for activation. This study investigates the potential for targeting the hypusine-polyamine (PA) nexus for cancer therapy. The study found that a combination of the DHPS inhibitor GC7 and the ODC inhibitor DFMO has synergistic antiproliferative effects in neuroblastoma (NB) cells. This approach could offer a new strategy for treating NB.
Paper Details　
Original Abstract of the Article :
The eukaryotic initiation factor 5A (eIF5A), which contributes to several crucial processes during protein translation, is the only protein that requires activation by a unique post-translational hypusine modification. eIF5A hypusination controls cell proliferation and has been linked to cancer. eIF...See full text at original site
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引用元：
https://doi.org/10.1042/BCJ20170597

データ提供：米国国立医学図書館（NLM）

A Synergistic Approach to Neuroblastoma Treatment: Targeting Hypusine-Spermidine Activation

Neuroblastoma, a type of cancer that affects the nervous system, presents a significant challenge in pediatric oncology. This study investigates a novel therapeutic approach that targets the hypusine-spermidine activation of eukaryotic initiation factor 5A (eIF5A), a crucial protein involved in protein translation. The authors demonstrate that a combination of GC7, a DHPS inhibitor, and DFMO, an ODC inhibitor, synergistically inhibits eIF5A activation, leading to apoptosis (programmed cell death) in neuroblastoma cells.

A Two-Pronged Attack: Targeting Hypusine-Spermidine Activation

The study's findings suggest that targeting the hypusine-spermidine activation pathway holds promise for treating neuroblastoma. It's like discovering a hidden weakness in the desert fortress, allowing for a more effective strategy to penetrate its defenses.

Combating Neuroblastoma: A Multi-faceted Approach

This research underscores the importance of exploring innovative therapeutic approaches for treating neuroblastoma. The study's findings suggest that targeting specific molecular pathways, such as hypusine-spermidine activation, may offer new avenues for effective cancer therapy. It's like utilizing a combination of tactics to navigate a challenging desert terrain, ensuring a successful journey.

Dr. Camel's Conclusion

This study presents a promising new approach to treating neuroblastoma by targeting the hypusine-spermidine activation of eIF5A. The synergistic effect of GC7 and DFMO in inducing apoptosis in neuroblastoma cells offers a compelling rationale for further research and development of targeted therapies for this challenging cancer. Just as a desert traveler seeks multiple sources of sustenance, we must continue to explore diverse approaches to combatting cancer and improve patient outcomes.

Date :
  1. Date Completed 2018-09-05
  2. Date Revised 2023-12-13
Further Info :

Pubmed ID

29295892

DOI: Digital Object Identifier

10.1042/BCJ20170597

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Languages

English

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