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Updated: Nov 9, 2025

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
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Adenosine Kinase Expression Determines DNA Methylation in Cancer Cell Lines

Amir E Wahba1, Denise Fedele1, Hoda Gebril1

  • 1Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey 08854, United States.

ACS Pharmacology & Translational Science
|April 16, 2021
PubMed

Insights

Adenosine kinase isoform ADK-L influences DNA methylation in cancer cells. Inhibiting ADK-L significantly reduces global DNA methylation, suggesting it as a therapeutic target for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • DNA methylation is crucial in cancer development and is targeted by therapies.
  • The transmethylation pathway, essential for DNA methylation, involves adenosine.
  • Adenosine kinase isoform with nuclear expression (ADK-L) is hypothesized to regulate global DNA methylation.

Purpose of the Study:

  • To investigate the role of ADK-L in determining global DNA methylation levels in cancer cells.
  • To assess the therapeutic potential of targeting ADK-L for manipulating DNA methylation in cancer.

Main Methods:

  • Quantification of ADK-L expression using Western Blot.
  • Measurement of global DNA methylation (percent 5-methyldeoxycytidine) via LC-MS/MS.
  • Treatment of cancer cell lines (HeLa, HepG2, U373) with ADK inhibitors (MRS4203, MRS4380).

Main Results:

  • ADK-L expression and global DNA methylation showed a positive correlation, highest in HeLa cells.
  • Potent ADK inhibitors significantly reduced global DNA methylation in HeLa cells in a dose-dependent manner.
  • A poor ADK inhibitor did not affect DNA methylation levels, confirming ADK specificity.

Conclusions:

  • ADK-L plays a significant role in regulating global DNA methylation in cancer cells.
  • ADK-L is a potential therapeutic target for modulating DNA methylation in cancer treatment.
  • Targeting ADK-L offers a novel strategy for cancer therapy by altering DNA methylation patterns.

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