Adriamycin inhibits embryonic development in zebrafish through downregulation of Kruppel-like factor4
I Syeda Thabassum Akthar1, P B Tirupathi Pichiah2, Sankarganesh Arunachalam3
1Department of Integrative Biology, School of Biosciences and Technology, VIT, Vellore, Tamilnadu, India.
Abstract:
Adriamycin is an effective anticancer drug used in a wide range of cancers. Anticancer drugs modulate oncogenes and nodal regulatory molecules that affect cell differentiation and organismal development. In this study, we explore the effect of adriamycin on Kruppel-like factor4 (Klf4), an essential pluripotent factor by choosing zebrafish embryos as a model system. Klf4 is involved in the regulation of cellular growth, proliferation, and differentiation. In zebrafish embryogenesis, Klf4 is a major regulator of differentiation of polster in the anterior mesendoderm region of cells into hatching gland cells. The importance of this study is to check the effect of adriamycin on embryonic development. We found, adriamycin dose dependently altered the gene expression level of Klf4 that occurs in parallel to its detrimental effect on hatching. Supportively, cathepsin L and cyclase-associated protein1 are the other two markers of hatching that are altered along with Klf4.
Insights
Adriamycin, an anticancer drug, disrupts zebrafish embryonic development by altering Kruppel-like factor 4 (Klf4) gene expression. This impacts hatching gland cell differentiation and hatching success in a dose-dependent manner.
Area of Science:
- Developmental Biology
- Pharmacology
- Genetics
Background:
- Adriamycin is a widely used anticancer drug.
- Anticancer drugs can affect oncogenes and regulatory molecules crucial for development.
- Kruppel-like factor 4 (Klf4) is a key factor in cellular pluripotency, growth, proliferation, and differentiation.
Purpose of the Study:
- To investigate the impact of adriamycin on embryonic development.
- To examine the effect of adriamycin on Kruppel-like factor 4 (Klf4) expression in zebrafish embryos.
Main Methods:
- Zebrafish embryos were used as a model system.
- The study analyzed the dose-dependent effects of adriamycin.
- Gene expression levels of Klf4 and hatching markers (cathepsin L, cyclase-associated protein1) were assessed.
Main Results:
- Adriamycin exposure altered Klf4 gene expression in a dose-dependent manner.
- The observed changes in Klf4 expression correlated with adverse effects on embryonic hatching.
- Expression of cathepsin L and cyclase-associated protein1, also hatching markers, were similarly affected.
Conclusions:
- Adriamycin interferes with embryonic development in zebrafish.
- Klf4 plays a critical role in zebrafish embryogenesis, specifically in hatching gland cell differentiation.
- Adriamycin's detrimental effects on hatching are linked to its modulation of Klf4 and other hatching-related genes.
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