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HPLC-based Assay to Monitor Extracellular Nucleotide/Nucleoside Metabolism in Human Chronic Lymphocytic Leukemia Cells
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Published on: July 20, 2016

Cerulenin-mediated apoptosis is involved in adenine metabolic pathway

Kyung-Sook Chung1, Nam-Kyu Sun, Seung-Hee Lee

  • 1Biopharmaceutical Division, KRIBB, 52 Oun-dong, Yusong-gu, Daejeon 305-806, Republic of Korea.

Biochemical and Biophysical Research Communications
|September 12, 2006
PubMed

Insights

Cerulenin, a fatty acid synthase inhibitor, triggers tumor cell death by disrupting adenine nucleotide biosynthesis. This leads to feedback inhibition and nuclear division defects in Schizosaccharomyces pombe.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Proteomics

Background:

  • Cerulenin is a fatty acid synthase (FAS) inhibitor known to induce apoptosis in various tumor cells.
  • Understanding the precise molecular mechanisms of cerulenin's action is crucial for its therapeutic potential.

Purpose of the Study:

  • To elucidate the mode of action of cerulenin using a proteomics approach.
  • To investigate the effects of cerulenin on protein expression and metabolic pathways in Schizosaccharomyces pombe.

Main Methods:

  • Proteomics analysis of Schizosaccharomyces pombe treated with cerulenin.
  • Differential protein expression profiling to identify modulated proteins.
  • Nutrient supplementation assays to assess metabolic pathway involvement.

Main Results:

  • Cerulenin modulated proteins involved in stress and metabolism, including ade10 and adk1.
  • Cerulenin disrupted enzymatic steps in phosphoribosyl group transfer, leading to AMP and AICAR accumulation.
  • Deregulation of adenine nucleotide biosynthesis caused feedback inhibition and transcriptional changes in metabolic pathways.

Conclusions:

  • Cerulenin induces apoptosis by deregulating adenine nucleotide biosynthesis.
  • This deregulation leads to defects in cell cycle progression and chromosome segregation.
  • Nuclear division defects in S. pombe are a consequence of cerulenin-induced metabolic disruption.

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