Related Experiment Video

Updated: May 23, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

Transient low doses of DNA-demethylating agents exert durable antitumor effects on hematological and epithelial tumor

Hsing-Chen Tsai1, Huili Li, Leander Van Neste

  • 1The Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

Cancer Cell
|March 24, 2012
PubMed

Insights

Low-dose decitabine and azacitidine treatments induce a sustained antitumor "memory" response in cancer cells. This approach reverses DNA hypermethylation and gene silencing, offering a promising new avenue for cancer therapy.

Area of Science:

  • Oncology
  • Epigenetics
  • Cancer Therapeutics

Background:

  • Reversing DNA hypermethylation and gene silencing is a key cancer therapy strategy.
  • Decitabine and azacitidine are DNA methylation inhibitors effective for hematological neoplasms at low doses.
  • High doses of these drugs cause cytotoxicity, but this doesn't explain the delayed patient response.

Purpose of the Study:

  • To investigate the effects of low-dose decitabine and azacitidine on cancer cells.
  • To determine if transient exposure can induce a lasting antitumor effect.
  • To explore the underlying epigenetic and cellular mechanisms of this response.

Main Methods:

  • Exposure of cultured and primary leukemic and epithelial tumor cells to nanomolar doses of decitabine and azacitidine.
  • Assessment of immediate cytotoxicity, DNA methylation levels, gene reexpression, and cellular regulatory pathways.
  • Evaluation of antitumor effects, including inhibition of cancer stem-like cells.

Main Results:

  • Transient, low-dose exposure without immediate cytotoxicity produced a sustained antitumor "memory" response.
  • Observed effects included inhibition of cancer stem-like cells.
  • Accompanied by sustained decreases in global promoter DNA methylation, gene reexpression, and beneficial changes in cellular regulatory pathways.

Conclusions:

  • Clinically relevant, low doses of decitabine and azacitidine can induce a durable antitumor effect.
  • This approach may overcome limitations of high-dose therapies and offers broad applicability in cancer management.
  • Further research into low-dose epigenetic therapy is warranted for various cancer types.

More Related Videos

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics12:28

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics

Published on: January 11, 2019

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Other Unique Bacteria01:18

Other Unique Bacteria

Magnetic bacteria exhibit a directed movement called magnetotaxis, driven by structures called magnetosomes. These magnetosomes consist of chains of magnetic particles made of either magnetite (Fe₃O₄) or greigite (Fe₃S₄) and are organized in a linear conformation by a protein scaffold within invaginations of the cell membrane. The bacteria align along the north–south magnetic field lines, much like a compass needle. They are typically microaerophilic or anaerobic and are commonly found near the...