Related Experiment Video

Updated: Aug 14, 2025

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage
10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

10.3K

Exploring pradimicin-IRD antineoplastic mechanisms and related DNA repair pathways

Larissa Costa de Almeida1, Felipe Antunes Calil2, Natália Cestari Moreno3

  • 1Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.

Chemico-Biological Interactions
|January 12, 2023
PubMed

Insights

This study reveals how pradimicin-IRD, a DNA-targeting agent, activates DNA repair pathways like nucleotide excision repair and double-strand break repair in cancer cells. Its TP53-independent action offers new anticancer chemotherapy insights.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Cancer Research

Background:

  • DNA-targeting agents are crucial in cancer chemotherapy but face toxicity challenges.
  • Understanding drug mechanisms and DNA damage responses can improve anticancer therapies.
  • Pradimicin-IRD is a novel DNA-targeting agent requiring further mechanistic study.

Purpose of the Study:

  • To investigate the DNA repair pathways activated by pradimicin-IRD in HCT 116 cells.
  • To elucidate the molecular interactions and cellular responses to pradimicin-IRD treatment.
  • To compare pradimicin-IRD's action with other DNA-targeting agents like doxorubicin.

Main Methods:

  • In silico molecular docking to predict drug-DNA and drug-protein interactions.
  • Transcriptomic analysis to identify modulated DNA repair genes.
  • Validation of gene expression changes and protein levels (PCNA, hTERT, POLH).
  • Assessment of cell resistance in POLH-deficient versus proficient cells.

Main Results:

  • Molecular docking identified pradimicin-IRD as a DNA intercalator and potential DNA-binding protein inhibitor.
  • Transcriptomics revealed modulation of nucleotide excision repair, telomere maintenance, and double-strand break repair genes.
  • PCNA protein levels decreased, suggesting DNA-pradimicin-PCNA interaction.
  • hTERT and POLH mRNA levels were reduced; POLH-deficient cells showed resistance to pradimicin-IRD.
  • Pradimicin-IRD's DNA repair gene modulation is TP53-independent, differing from doxorubicin.

Conclusions:

  • Pradimicin-IRD activates specific DNA repair pathways, including those involving PCNA, hTERT, and POLH.
  • The TP53-independent mechanism distinguishes pradimicin-IRD from doxorubicin, suggesting unique therapeutic potential.
  • Further research into pradimicin-IRD as an antineoplastic compound is warranted.
Keywords:
CancerDNA damageDNA repairDNA-targeting agentDoxorubicinPradimicin-IRD

More Related Videos

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays04:07

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays

Published on: February 24, 2023

1.8K
Visualization of DNA Repair Proteins Interaction by Immunofluorescence07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.3K

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
Overview of DNA Repair02:25

Overview of DNA Repair

7.7K
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...
6.7K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.5K