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High Throughput Microinjections of Sea Urchin Zygotes
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Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models

Tamara Babic1, Jelena Dinic2, Sonja Stojkovic Buric2

  • 11 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade , Vojvode Stepe 444a, 11010, Belgrade , Serbia.

Acta Biologica Hungarica
|December 28, 2018
PubMed

Insights

Targeted cancer therapy inhibitors showed varying toxicity in early development. AZD2014, a dual mTOR inhibitor, demonstrated significant promise for anticancer therapy due to its selective toxicity.

Area of Science:

  • Pharmacology
  • Developmental Biology
  • Cancer Research

Background:

  • Cancer drug resistance and poor selectivity necessitate novel therapeutics.
  • PI3K-Akt-mTOR and RAS-MAPK-ERK pathways are crucial in cell functions and cancer development.
  • Deregulation of these pathways contributes to therapy resistance.

Purpose of the Study:

  • To evaluate the toxicity of targeted pathway inhibitors on early zebrafish and sea urchin development.
  • To assess the potential of these inhibitors as anticancer agents by examining their effects on normal, fast-proliferating cells.

Main Methods:

  • Investigated effects of wortmannin, GSK690693, AZD2014, and tipifarnib on early development.
  • Assessed toxicity and impact on embryo survival and development in zebrafish and sea urchins.
  • Compared inhibitor effects on embryonic cells versus cancer cells.

Main Results:

  • Wortmannin (PI3K inhibitor) and tipifarnib (RAS inhibitor) showed highest toxicity.
  • GSK690693 (pan-Akt inhibitor) had a less significant impact.
  • Combined PI3K-Akt-mTOR inhibition (wortmannin/GSK690693) showed synergistic toxicity.
  • AZD2014 (dual mTOR inhibitor) exhibited low toxicity in embryonic models but high toxicity in cancer cells, with minimal effects on normal cells.

Conclusions:

  • AZD2014 displays selective toxicity towards cancer cells, making it a promising candidate for anticancer therapy.
  • Its ability to sensitize resistant cancers and low antiproliferative activity against normal cells supports its therapeutic potential.
  • Further investigation into AZD2014 is warranted for its development as a novel cancer treatment.
Keywords:
AZD2014PI3K-Akt-mTOR signaling pathwayRAS-MAPK-ERK signaling pathwaysea urchin ()zebrafish ()

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