Related Experiment Video

Updated: Aug 11, 2026

Tools to Study the Role of Architectural Protein HMGB1 in the Processing of Helix Distorting, Site-specific DNA Interstrand Crosslinks
12:19

Tools to Study the Role of Architectural Protein HMGB1 in the Processing of Helix Distorting, Site-specific DNA Interstrand Crosslinks

Published on: November 10, 2016

Poly (ADP-ribose) polymerase inhibitor increases apoptosis and reduces necrosis induced by a DNA minor groove binding

L Tentori1, A Balduzzi, I Portarena

  • 1Pharmacology and Medical Oncology Section, Department of Neuroscience, University of Rome Tor Vergata, Via di Tor Vergata 135, 00133 Rome, Italy.

Cell Death and Differentiation
|August 30, 2001
PubMed

Insights

Poly(ADP-ribose) polymerase (PARP) inhibitors alter cell death pathways. Combining a PARP inhibitor with a methylating agent (Me-Lex) promoted apoptosis and reduced necrosis in leukemia cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Poly(ADP-ribose) polymerase (PARP) plays a crucial role in DNA repair mechanisms, particularly in response to DNA damage like N3-adenine methylation.
  • Base excision repair is activated by DNA damage, and PARP is integral to this cellular recovery process.

Purpose of the Study:

  • To investigate the effects of a specific methylating agent, MeOSO(2)(CH(2))(2)-lexitropsin (Me-Lex), on human leukemic cell death.
  • To determine how the presence of a PARP inhibitor influences the cell death modalities induced by Me-Lex.

Main Methods:

  • Treatment of human leukemic cell lines with Me-Lex alone and in combination with a PARP inhibitor.
  • Analysis of cell death pathways, including apoptosis and necrosis.
  • Assessment of c-myc expression, DNA single-strand breaks, and telomerase activity.

Main Results:

  • Me-Lex alone induced primarily necrosis at high concentrations, while its combination with a PARP inhibitor led to growth inhibition, c-myc down-regulation, increased single-strand breaks, and enhanced apoptosis.
  • Surprisingly, the PARP inhibitor reduced the early onset of necrosis induced by Me-Lex.
  • Telomerase activity was initially suppressed by Me-Lex alone but not when combined with the PARP inhibitor, with inhibition observed later in both treatment groups.

Conclusions:

  • High levels of N3-methyladenine induce distinct cell death modalities.
  • PARP inhibition significantly alters the cellular response to N3-methyladenine, shifting the balance towards apoptosis and away from necrosis.
  • These findings provide new insights into the complex interplay between DNA damage, repair pathways, and cell fate in cancer therapy.

More Related Videos

Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery08:09

Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery

Published on: August 6, 2019

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors06:07

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

Published on: August 5, 2022

Related Concept Videos

Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...